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>>IT'S MY PLEASURE TO WELCOME


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YOU TO FLORENCE MAHONY

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BASED ON HER OUTSTANDING

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GROUND-BREAKING WORK ON STUD'S

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OF THE COLOMBIA YAN KINDRED WITH

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AUTOSOMAL ALZHEIMER'S DISEASE.

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THEY'RE IN MEMORY OF FLORENCE

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MAHONEY.

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SHE SPENT HER LIFE PROMOTING NIH

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AND NATIONAL INSTITUTE ON AGING

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UNTIL HER DEATH AT AGE OF 103

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AND UP UNTIL THAT TIME, I WOULD

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MEET WITH HER EACH YEAR AND SHE

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WONDERED WHO WOULD GIVE THE

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LECTURE AND SHE WANTED NO

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NONSENSE.

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ONE OF THE MOST CUTTING EDGE BUT

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ALSO RIGOROUS SCIENTIST AND SHE

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WOULD BE THRILLED TO SEE OUR

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TRADITION BEING KEPT UP TODAY

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SO, TO INTRODUCE YOU SHE BEGAN

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HER CAREER WITH HER

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UNDERGRADUATE EDUCATION AT THE

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ANTI-OPENNIA WHERE THE KINDRED

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HAS BECOME A FOCUS OF HER STUDY

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AND HAS ORIGINATED AND SHE WENT

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TO BOSTON UNIVERSITY FOR BOTH

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HER MASTERS AND PH.D DEGREE IN

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CLINICAL NEUROSCIENCE.

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MOVED TO MASS GENERAL WHERE SHE

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HAS NOW ADVANCED TO THE LEVEL OF

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ASSOCIATE PROFESSOR IN THE

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DEPARTMENT OF NEUROLOGY AND

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PSYCHOLOGY.

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SHE'S BEEN HONORED BY MULTIPLE,

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INCLUDING THE NIH EARLY

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INDEPENDENCE AWARD OF ONE WHICH

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ENCOURAGES PEOPLE WITH HIGH

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PROMISE, EARLY IN THEIR CAREER

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TO MOVE FORWARD WITH

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INDEPENDENCE AND A GREAT HONOR

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IN DEED.

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HONORS BY THE ALZHEIMER'S

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ASSOCIATION AND MGH AND TODAY

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WE'LL HAVE AN OPPORTUNITY TO

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HEAR ABOUT HER ABOUT THIS GROUND

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BREAKING WORK.

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I ENCOURAGE YOU TO HAVE YOUR

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QUESTIONS READY FOR HER AND

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WE'LL BE BACK WITH THEM AT THE

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END OF HER TALK.

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 [APPLAUSE]

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>> THANK YOU FOR THE KIND

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INTRODUCTION AND ALSO FOR THE

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INVITATION TO PRESENT OUR WORK.

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IT'S REALLY AN HONOR TO GIVE

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THIS LECTURE AND FLORENCE

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MAHONEY'S WORK SO THANK YOU FOR

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THE OPPORTUNITY.

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I'M GOING TO SHARE SOME OF THE

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WORK WE'VE BEEN DOING WITH THE

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COLOMBIA KINDRED AND IT'S A

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DISEASE AND IT WAS MENTIONED

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BEFORE SO MY NAME IS Dr.

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QUIROZ FROM THE MASSACHUSETTS

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GENERAL HOSPITAL.

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I WEAR SEVERAL HATS.

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BEFORE I MOVED TO THE COLOMBIA

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YAN KINDRED IT WAS BASED ON A

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CONVERSATION I HAD.

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THIS MORNING, THANK YOU TO

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EVERYBODY WHO GOT ON TIME TO

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MEET WITH THIS MORNING AND IT'S

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A BIG THANK YOU TO KIM FOR

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ORGANIZING ALL THE LOGISTICS FOR

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THIS MEETING AND I APPRECIATE

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IT.

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SO, I WILL HAVE THE MULTI

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CULTURAL SCIENCE PROGRAM AND

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THEY'RE GOING TO BE MENTIONED

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THESE ARE IN THE PRESENTATION

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BUT I WANT YOU TO MENTION THAT

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I'M VERY STRONG AND VERY

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COMMITTED TO INCREASING THE

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PRESENTATION OF WOMEN AND OTHER

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UNDER REPRESENTED MINORITIES

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GROUPS IN RESEARCH AND SCIENCE

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AND WE TRIED TO FOLLOW THE

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CULTURAL DIVERSION PREVENTION

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AND JUST LAST MONTH, WE WROTE

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THIS PERSPECTIVE REVIEW PAPER SO

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I INVITE YOU TO, IF YOU ARE

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INTERESTED IN THIS TOPIC, TO

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TAKE A LOOK AND LEARN MORE ABOUT

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THE WORK WE'RE DOING AND

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DIVERSITY AND CREASING DIVERSITY

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IN CLINICAL CARE AND RESEARCH.

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WITH THAT SAID, I'M GOING TO

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MOVE TO THE TOPIC FOR TODAY.

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IT'S GOING TO BE BASED ON THE

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ALZHEIMER'S DISEASE.

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SO FOR THE OUTLINE, WE'LL START

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WITH AN OVERVIEW WHERE WE KNOW

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ALZHEIMER'S DISEASE AND WE'RE

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TALKING ABOUT SOME OF THE EARLY

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THINGS WE HAVE WITH MUTATION

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CARRIERS AND MOVING TO SOME OF

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THE WORK WITH THE COLOMBIA

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BOSTON YAN STUDY WITH THE

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PATHOLOGY AND ALZHEIMER'S

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DISEASE AND THEN DISCUSS WHAT WE

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HAVE LEARNED ABOUT COGNITIVE

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BIOMARKERS ESPECIALLY IN BRIEFLY

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MENTIONED IN THE WORK THAT WE

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HAVE DURING THE PAST FEW YEARS

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WITH REMOTE AND THE BIO MACKERS

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AND LASTLY SOME OF THE WORK WITH

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THE COLBOS EXTREME IN RESILIENCE

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IN THE KINDRED.

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AND JUST TO MAKE SURE THAT

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EVERYBODY -- I KNOW YOU ARE

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FAMILIAR WITH THIS BUT JUST TO

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MAKE SURE THAT EVERYBODY IS ON

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THE SAME PAGE AS REMINDERS SO

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THE MOST COMMON FORM OF

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ALZHEIMER'S DISEASE IS ONSET

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ALZHEIMER'S DISEASE THIS IS

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EXPLAINS THE CASES.

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USUALLY WE THEY WILL THEY HAVE A

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SYMPTOMS OR THE AGE OF 65 AND

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THERE ARE SOME IMPORTANT RACE

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FACTORS, OLDER AGE ARE THE MOST

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IMPORTANT ONE BUT FOLLOWED BY

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FAMILY HISTORY AND ALSO WE KNOW

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THAT THE MAIN RISK FACTOR IS

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APOE4 AND THERE'S ANOTHER ONE WE

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CALL FAMILIAR ALZHEIMER'S

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DISEASE AND IT'S ONLY ON

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MINORITY OF CASES AND IT'S

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USUALLY EXPLAINED BY ALZHEIMER'S

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MUTATIONS IN THREE MAIN GENES

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THAT ARE PRESENTING.

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ONE PRESENT IT WOULD GO AND APP

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GENES AND DIFFERENT FROM THIS

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ONSET ALZHEIMER'S DISEASE, IT'S

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USUALLY DEVELOPED AND

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ALZHEIMER'S DISEASE BEFORE THE

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AGE OF 65 AND THIS MUTATIONS ARE

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NEARLY HIGHLY PENETRANTS AND PED

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THEY HAVE CLINICAL ONSET AND YOU

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ARE FAMILIAR WITH THIS SO WE'RE

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MOVING TO THE DEFINITION OF

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ALZHEIMER'S.

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THE LAST PHASE IS D DEMENTIA AND

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THE CURRENT READINGS ARE

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DEVELOPED BETWEEN WHEN THEY

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ALREADY HAVE SYMPTOMS AND ALL

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THE WORK THAT WE HAVE DID NOT

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DOING IN THE PAST SEVERAL YEARS

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HAS BEEN TRYING TO IDENTIFY THE

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CLINICAL STAGE AND ONE OF THE

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GOALS ORIENTED TO FINDING THIS

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IS TO BE ABLE TO DELAY THE

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CLINICAL ONSET AND OF COURSE IN

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THE FUTURE BE ABLE TO PREVENT

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ALZHEIMER'S AND DEMENTIA BOTH

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TOGETHER.

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ONE OF THE GOALS OF THIS

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PREVENTION WERE IS THE CLINICAL

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DETECTION OF ALZHEIMER'S IS TO

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ACTUALLY BE ABLE TO INITIATE

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TREATMENT AS EARLY AS POSSIBLE

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SO THEY HAVE THE BEST POSSIBLE

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OUTCOME.

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AND TOGETHER WITH THE

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TREATMENTS, WE ALSO HAVE THE

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POSSIBILITY OF BEING ABLE TO

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PREVENT ALZHEIMER'S DISEASE ALL

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TOGETHER IN THE FUTURE.

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ONE WAY THAT WE HAVE BEEN USING

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TO ACTUALLY DETECT ALZHEIMER'S

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DISEASE AS EARLY AS POSSIBLE IS

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THROUGH BY BIOMARKERS AND AS YOU

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MAY KNOW AS WELL SO BIOMARKERS

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GIVE YOU THE CHANCE TO DETECT

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ALZHEIMER'S DISEASE OR ANY

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DISEASE AND GIVE YOU A CHANCE TO

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STAY THE DISEASE AND MONITOR THE

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DISEASE AND CLINICAL TRIALS GIVE

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YOU A CHANCE TO MONITOR THE

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RESPONSE TO TREATMENTS.

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THERE ARE SEVERAL BIOMARKERS

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VALIDATION AND HERE I'M SHOWING

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SOME OF THE BIOMARKERS THAT WE

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ARE CURRENTLY PURSUING AT SOME

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POINT AND BIOMARKERS USING IMAGE

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ARE FOR ATROPHY, AND TAU, AND

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BIOMARKERS THAT ARE DEVELOPED

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FOR NEURO INFLAMMATION AND WHEN

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YOU TALK WITH BIOMARKERS, THERE

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ARE TWO WAYS TO GO ABOUT

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BIOMARKERS.

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ONE, YOU CAN HAVE THOSE THAT ARE

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AT INCREASED RISK TO DEVELOP

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ALZHEIMER'S IN THIS CASE LATE

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ONSET ALZHEIMER'S.

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OR YOU CAN ALSO GO ABOUT

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ALZHEIMER'S DISEASE AND AS YOU

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ALREADY KNOW BY THE TALK ON THE

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PRESENTATIONS, THIS IS THE WAY

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THAT WE HAVE BEEN WORKING OUT

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THESE BIOMARKERS.

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THIS IS SOMETHING THAT WE HAVE

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BEEN DOING FOR SEVERAL YEARS SO

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IT WAS SOMETHING THAT FRANCIS,

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THE GUY HERE IN THE PICTURE,

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STARTED DOING 30 YEARS IN

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COLOMBIA.

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IN COLOMBIA WE HAVE FAMILIES WE

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HAVE MANY DISEASE ALZHEIMER'S

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AND HUNTINGTON AND CADASIL AND I

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JOIN HIS GROUP WHEN I WAS IN

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COLLEGE SO FOR ME, A LITTLE OVER

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20 YEARS AND SINCE THEN, I HAVE

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BEEN WORKING WITH HIM IN THIS

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PROJECT CHARACTERIZING THESE

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FAMILIES.

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SO MY MAIN CONTRIBUTION TO THE

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WORK OF THE GROUP IN COLOMBIA

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HAS BEEN MOSTLY FOR BIOMARKERS.

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HELPING TO GET THE FAMILIES

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READY SO JUST REMIND YOU A

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LITTLE BIT, TELL YOU A LITTLE

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BIT ABOUT THESE FAMILIES THAT WE

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FOLLOW, SO THE ONES WITH

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ALZHEIMER'S DISEASE, WE HAVE THE

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WORLD'S LARGEST EXTENDED FAMILY

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WITH A SINGLE GENETIC MUTATION

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FOR EARLY ALZHEIMER'S DISEASE

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AND WE HAVE A LITTLE BIT OVER

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6,000 INDIVIDUALS THAT CARRY A

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SINGLE DNA MUTATION AND THIS IS

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THE E288 MUTATION.

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AND INDIVIDUALS THAT CARRY THIS

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MUTATION THEY DEVELOP COGNITIVE

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IMPAIRMENT ABOUT THE AGE OF 44

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AND DEMENTIA AT THE AGE OF 49.

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THERE ARE SEVERAL SIMILARITIES

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BETWEEN THESE FORM OF THE

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DISEASE AND THE MOST COMMON FORM

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OF THE DISEASE AT LEAST IS THE

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LATE ONSET AND IT'S BETWEEN THE

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TWO TYPES.

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THERE'S A OPPORTUNITY TO SAY

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THESE FAMILIES GIVE YOU AN

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OPPORTUNITY TO SEW INDIVIDUALS

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THAT ARE DESTIN TO DEVELOP

258
00:09:55,280 --> 00:09:58,600
ALZHEIMER'S AND DEMENTIA IN THE

259
00:09:58,600 --> 00:10:00,640
FUTURE BUT WITH SEVERAL YEARS OR

260
00:10:00,640 --> 00:10:03,400
DECADES BEFORE THEY HAVE ANY

261
00:10:03,400 --> 00:10:05,720
SYMPTOMS, SO WE HAVE A WINDOW OF

262
00:10:05,720 --> 00:10:06,880
OPPORTUNITY TO CHARACTERIZE SOME

263
00:10:06,880 --> 00:10:09,320
OF THE CLINICAL CHANGES RELATED

264
00:10:09,320 --> 00:10:13,160
TO ALZHEIMER'S DISEASE.

265
00:10:13,160 --> 00:10:15,080
AND THIS IS ONE OF THE FIRST

266
00:10:15,080 --> 00:10:18,280
QUESTIONS THAT I HAVE BEEN IN

267
00:10:18,280 --> 00:10:20,440
ANSWERING AND WORKING ON THAT SO

268
00:10:20,440 --> 00:10:22,520
WHAT ARE THE EARLY BIOLOGICAL

269
00:10:22,520 --> 00:10:24,520
AND PHYSIOLOGICAL CHANGES

270
00:10:24,520 --> 00:10:27,400
ASSOCIATED WITH THE POSITION TO

271
00:10:27,400 --> 00:10:27,760
ALZHEIMER'S.

272
00:10:27,760 --> 00:10:30,240
AND TO START ANSWERING THAT

273
00:10:30,240 --> 00:10:32,040
QUESTION, THE FIRST SET OF THE

274
00:10:32,040 --> 00:10:34,720
STUDIES WE DID WAS USING A

275
00:10:34,720 --> 00:10:37,640
FUNCTION MRI.

276
00:10:37,640 --> 00:10:40,280
THIS IS SOME OF THE WORK THAT I

277
00:10:40,280 --> 00:10:43,320
DID WHEN I WAS A PH.D STUDENT, I

278
00:10:43,320 --> 00:10:46,920
STUDENTS MRI TO DECIDE BRAIN ACT

279
00:10:46,920 --> 00:10:51,800
EVACUAACTIVATION WHEN THE BRAIN

280
00:10:51,800 --> 00:10:54,440
CARRIERS ARE THE SIBLINGS AND IT

281
00:10:54,440 --> 00:10:55,880
LEARNING NEW FACE NAMES WHEN

282
00:10:55,880 --> 00:10:58,880
THEY WERE IN THIS AND THE FIRST

283
00:10:58,880 --> 00:11:00,320
WAS THIS ONE IT WAS OLDER

284
00:11:00,320 --> 00:11:03,200
CARRIERS AND COLDER THAN 25.

285
00:11:03,200 --> 00:11:05,280
WHEN WE COMPARED THE LEARNING

286
00:11:05,280 --> 00:11:08,040
DURING THE YOUNGER AND THE

287
00:11:08,040 --> 00:11:10,600
REPEATED NAMES WE FOUND THE

288
00:11:10,600 --> 00:11:14,080
CARRIERS ACTUAL LOW HAD HYPO CAM

289
00:11:14,080 --> 00:11:15,840
PA ACTIVATION COMPARED TO THE

290
00:11:15,840 --> 00:11:17,640
NON CARRIERS AND IT WAS ALREADY

291
00:11:17,640 --> 00:11:19,440
TELLING US THEY HAVE SOME BRAIN

292
00:11:19,440 --> 00:11:21,080
I AM NORMALITIES IN BRAIN

293
00:11:21,080 --> 00:11:23,280
FUNCTION OR IN THIS CASE

294
00:11:23,280 --> 00:11:24,880
LEARNING FACE NAMES.

295
00:11:24,880 --> 00:11:26,920
THEN I DECIDED TO GO YOUNGER SO

296
00:11:26,920 --> 00:11:29,920
WE WENT TO 18-25 AND WE DID THE

297
00:11:29,920 --> 00:11:31,120
SAME TASK.

298
00:11:31,120 --> 00:11:32,840
THEY WERE USING THE SAME FACE

299
00:11:32,840 --> 00:11:35,440
NAME TASK AND THEN WE ACTUALLY

300
00:11:35,440 --> 00:11:40,360
SAW THAT IN ADDITION INFORM THIS

301
00:11:40,360 --> 00:11:42,800
HYPER ACTIVATION THEY HAVE HYPER

302
00:11:42,800 --> 00:11:44,600
ACTIVATION IN OTHER REGIONS AND

303
00:11:44,600 --> 00:11:46,840
OTHER REGIONS OF THE GAME SO

304
00:11:46,840 --> 00:11:49,440
PRETTY MUCH THERE WAS STILL SO

305
00:11:49,440 --> 00:11:50,120
ABNORMALITIES IN THE CARRIERS

306
00:11:50,120 --> 00:11:52,640
COMPARED TO A NON CARRIER AND

307
00:11:52,640 --> 00:11:55,120
THEN, I WENT EVEN YOUNGER AND

308
00:11:55,120 --> 00:11:56,720
INCREASED IN CHILDREN THIS CASE

309
00:11:56,720 --> 00:11:59,400
INDIVIDUALS FROM 9 YEARS TO 18

310
00:11:59,400 --> 00:12:00,960
YEARS, AND THEN THE FIRST THING

311
00:12:00,960 --> 00:12:04,120
WE FOUND IT WAS THERE WAS NO

312
00:12:04,120 --> 00:12:07,960
DIFFERENCE IN THE TEMPORAL LOBE

313
00:12:07,960 --> 00:12:09,080
BETWEEN CARRIERS AND NON

314
00:12:09,080 --> 00:12:11,600
CARRIERS AND WE SAW THIS TYPIER

315
00:12:11,600 --> 00:12:12,760
ACTIVATION IN THE CARRIERS

316
00:12:12,760 --> 00:12:16,040
COMPARED TO A NON-CARRIER AND WE

317
00:12:16,040 --> 00:12:20,520
CALL HERE LESS ACTIVATION OF

318
00:12:20,520 --> 00:12:22,200
REGIONS AND WE DON'T EXPECT THIS

319
00:12:22,200 --> 00:12:24,520
ACTIVATION DURING THIS TASK SO

320
00:12:24,520 --> 00:12:26,560
THIS THREE EXPERIMENTS TELLING

321
00:12:26,560 --> 00:12:29,080
US THERE WERE ABNORMALITIES IN

322
00:12:29,080 --> 00:12:31,240
THE CARRIERS SEVERAL YEARS

323
00:12:31,240 --> 00:12:33,680
BEFORE THEY HAVE ANY KIND OF

324
00:12:33,680 --> 00:12:34,320
SYMPTOMS.

325
00:12:34,320 --> 00:12:38,120
THEN I STARTED LOOKING AT

326
00:12:38,120 --> 00:12:40,600
STRUCTURE AND THE NEXT WAS

327
00:12:40,600 --> 00:12:41,920
CORTICAL THICKNESS AND THE OLDER

328
00:12:41,920 --> 00:12:43,400
CARRIERS AND WE FOUND THAT THE

329
00:12:43,400 --> 00:12:44,960
CARRIERS COMPARED TO THE NON

330
00:12:44,960 --> 00:12:48,480
CARRIERS, THEY ACTUALLY HAVE

331
00:12:48,480 --> 00:12:50,320
CORTEX IN THE REGIONS AND FEW

332
00:12:50,320 --> 00:12:53,000
YEARS BEFORE SYMPTOMS AND THEN I

333
00:12:53,000 --> 00:12:56,520
USED ERP THAT IS POTENTIAL SO

334
00:12:56,520 --> 00:12:58,560
BASED ON EEG IN THIS CASE AND

335
00:12:58,560 --> 00:13:01,080
THE CARRIERS ALSO HAVE

336
00:13:01,080 --> 00:13:02,680
ABNORMALITIES IN EXTERIOR

337
00:13:02,680 --> 00:13:04,240
REGIONS WHEN THEY WERE LEARNING

338
00:13:04,240 --> 00:13:07,520
COMPARED TO THE NON CARRIERS.

339
00:13:07,520 --> 00:13:09,120
SO THIS FIVE EXPERIMENTS ALL

340
00:13:09,120 --> 00:13:10,720
TOGETHER PROVIDE SOME OF THE

341
00:13:10,720 --> 00:13:13,840
FIRST AREAS TO BE BRAIN CHANGES

342
00:13:13,840 --> 00:13:15,080
IN COGNITIVELY TO INDIVIDUALS

343
00:13:15,080 --> 00:13:17,680
MANY YEARS BEFORE CLINICAL

344
00:13:17,680 --> 00:13:17,880
ONSET.

345
00:13:17,880 --> 00:13:23,200
AFTER ALL THIS IS DONE, WE START

346
00:13:23,200 --> 00:13:25,600
AND WE USE ALL BIOMARKERS

347
00:13:25,600 --> 00:13:28,240
INCLUDING BIOMARKERS IN CSF AND

348
00:13:28,240 --> 00:13:31,520
THE FIRST STUDY WE DID FOR AM

349
00:13:31,520 --> 00:13:34,240
LLOYD AND PUTTING ALL THE

350
00:13:34,240 --> 00:13:36,480
MARKERS TOGETHER, IN THIS AGE

351
00:13:36,480 --> 00:13:38,200
RELATED TRAJECTORY ACTUALLY

352
00:13:38,200 --> 00:13:40,160
OBSERVED THAT THE FIRST

353
00:13:40,160 --> 00:13:42,600
ABNORMALITIES IN THIS INDIVIDUAL

354
00:13:42,600 --> 00:13:45,680
ARE SHOWED BEFORE, THE EARLIEST

355
00:13:45,680 --> 00:13:50,080
ABNORMALITIES THAT WERE SEEN

356
00:13:50,080 --> 00:13:54,720
WERE CHANGES IN AMALIOI AND AS

357
00:13:54,720 --> 00:13:57,440
EARLY AS IN THE EARLY 20s.

358
00:13:57,440 --> 00:14:00,320
SO, ONE OF THE FIRST QUESTIONS

359
00:14:00,320 --> 00:14:03,800
YOU WILL SEE THAT IN THIS

360
00:14:03,800 --> 00:14:04,360
PRESENTATION I HAVE MORE

361
00:14:04,360 --> 00:14:06,040
QUESTIONS THAN ANSWERS, ONE OF

362
00:14:06,040 --> 00:14:08,400
THE FIRST QUESTIONS THAT I HAVE

363
00:14:08,400 --> 00:14:11,280
OF THIS IS PRETTY MUCH NOW THAT

364
00:14:11,280 --> 00:14:13,000
WE HAVE EVIDENCE OF THIS

365
00:14:13,000 --> 00:14:14,480
ABNORMALITIES, SO WE KNOW THERE

366
00:14:14,480 --> 00:14:16,120
ARE ABNORMALITIES IN BRAIN

367
00:14:16,120 --> 00:14:17,480
FUNCTION BUT WHAT ARE ACTUALLY

368
00:14:17,480 --> 00:14:21,000
THE EARLIEST ABNORMALITIES AND

369
00:14:21,000 --> 00:14:22,440
IT'S ACTUALLY WITH ANOTHER

370
00:14:22,440 --> 00:14:24,120
COUPLE OF QUESTIONS THAT I STILL

371
00:14:24,120 --> 00:14:26,960
DON'T HAVE THE ANSWER AND IT'S

372
00:14:26,960 --> 00:14:28,800
LIKE ARE THERE ANY NEURO

373
00:14:28,800 --> 00:14:29,320
DEVELOPMENTAL DIFFERENCES

374
00:14:29,320 --> 00:14:31,040
BETWEEN THE CARRIERS AND THE NON

375
00:14:31,040 --> 00:14:31,560
CARRIERS?

376
00:14:31,560 --> 00:14:34,280
I MEAN IN CASE THERE ARE NEURO

377
00:14:34,280 --> 00:14:35,200
DEVELOPMENTAL CHANGES DUE TO

378
00:14:35,200 --> 00:14:39,240
THIS MUTATION, ARE THESE

379
00:14:39,240 --> 00:14:40,960
CONTRIBUTING TO FUTURE COGNITIVE

380
00:14:40,960 --> 00:14:44,720
DECLINE IN THE CARRIERS AND THE

381
00:14:44,720 --> 00:14:46,520
ANSWER TO THIS QUESTION WHICH I

382
00:14:46,520 --> 00:14:48,800
STILL DON'T HAVE THE ANSWER.

383
00:14:48,800 --> 00:14:51,760
I WANT TO BRING YOUR ATTENTION

384
00:14:51,760 --> 00:14:54,080
BACK TO THE CHILDREN STUDY WHEN

385
00:14:54,080 --> 00:14:56,880
IN ADDITION TO THE ABNORMAL

386
00:14:56,880 --> 00:14:59,920
ACTIVITY DURING TASK RELATED TO

387
00:14:59,920 --> 00:15:02,800
THE MRI WE FOUND ABNORMALITIES

388
00:15:02,800 --> 00:15:04,560
AND RESTING STATE NETWORK AS

389
00:15:04,560 --> 00:15:07,720
SEEN HERE AND WE FOUND INCREASED

390
00:15:07,720 --> 00:15:09,560
CONNECTIVITY BETWEEN THE POSTER

391
00:15:09,560 --> 00:15:15,880
YEAR REGIONS AND THE TEMPORAL

392
00:15:15,880 --> 00:15:18,040
AND WE HAVE GRAY MATTER VOLUME

393
00:15:18,040 --> 00:15:19,720
IN TEMPORAL REGIONS IN THE

394
00:15:19,720 --> 00:15:21,760
CARRIERS COMPARED TO NON

395
00:15:21,760 --> 00:15:22,160
CARRIERS.

396
00:15:22,160 --> 00:15:24,720
EVEN A 90-YEARS-OLD, THE

397
00:15:24,720 --> 00:15:26,720
YOUNGEST ONES THAT WE HAVE, WE

398
00:15:26,720 --> 00:15:29,120
ARE SEEING THESE DEVELOPMENTAL

399
00:15:29,120 --> 00:15:31,280
CHANGES IN THE CARRIERS COMPARED

400
00:15:31,280 --> 00:15:36,000
TO FINANON CARRIERS.

401
00:15:36,000 --> 00:15:37,960
HAVING ALL THE IMAGING WE HAVE

402
00:15:37,960 --> 00:15:41,240
WITH THIS INDIVIDUALS, SO

403
00:15:41,240 --> 00:15:44,680
TOGETHER ONE OF MY PH.D STUDENTS

404
00:15:44,680 --> 00:15:46,440
ACTUALLY PUT ALL THIS DATA

405
00:15:46,440 --> 00:15:48,080
TOGETHER AND WE STARTED LOOKING

406
00:15:48,080 --> 00:15:49,480
AT THE LIFESPAN AND THIS IS ONE

407
00:15:49,480 --> 00:15:52,160
OF THE FIRST ATTEMPTS TO LOOK AT

408
00:15:52,160 --> 00:15:56,600
DATA ALL TOGETHER AND WE PUT

409
00:15:56,600 --> 00:15:58,320
TOGETHER 200MRIs THAT WE HAVE

410
00:15:58,320 --> 00:15:59,640
THAT EVERYBODY THAT I SHOWED

411
00:15:59,640 --> 00:16:01,400
BEFORE AND THIS IS KIND OF LIKE

412
00:16:01,400 --> 00:16:03,280
WHAT WE FOUND IS VERY

413
00:16:03,280 --> 00:16:04,840
INTERESTING, WE FOUND THAT

414
00:16:04,840 --> 00:16:08,160
THEY'VE TAKEN IT'S THE FIRST

415
00:16:08,160 --> 00:16:14,920
MEASURE WE ENCLOUD HERE IT'S

416
00:16:14,920 --> 00:16:16,400
FLUCTUATING ALONG THE LIFESPAN

417
00:16:16,400 --> 00:16:22,680
AND WE FOUND TWO POINTS THAT WAS

418
00:16:22,680 --> 00:16:25,080
CLEAR AT THE AGE OF 17 AND ONE

419
00:16:25,080 --> 00:16:26,920
AT THE AGE OF 32 WHEN THEY

420
00:16:26,920 --> 00:16:28,840
STARTED DECLINING UNTIL THEY

421
00:16:28,840 --> 00:16:32,520
STARTED DEVELOPING MCI AND

422
00:16:32,520 --> 00:16:33,360
DEMENTIA.

423
00:16:33,360 --> 00:16:34,640
I WAS STILL VERY INTRIGUED AND I

424
00:16:34,640 --> 00:16:38,040
WAS GOING ON HERE BEFORE THE AGE

425
00:16:38,040 --> 00:16:39,880
OF 17.

426
00:16:39,880 --> 00:16:42,360
WE WENT AND TOGETHER WITH MY

427
00:16:42,360 --> 00:16:44,600
PH.D STUDENT AND ANOTHER PH.D

428
00:16:44,600 --> 00:16:46,600
STUDENT, WE WENT INTO THE

429
00:16:46,600 --> 00:16:48,200
COGNITION AND WE COLLECTED DATA

430
00:16:48,200 --> 00:16:50,720
IN THIS CASE IN OVER 1,000

431
00:16:50,720 --> 00:16:52,800
CHILDREN FROM THE KINDRED, USING

432
00:16:52,800 --> 00:16:56,400
THIS MEASURE THAT IS ONE OF THE

433
00:16:56,400 --> 00:16:58,080
FIRST MEASURES AVAILABLE AND WE

434
00:16:58,080 --> 00:16:59,320
DIDN'T FIND DIFFERENCE BETWEEN

435
00:16:59,320 --> 00:17:00,960
THE CARRIERS AND THE NON

436
00:17:00,960 --> 00:17:03,320
CARRIERS BUT WHEN WE STARTED

437
00:17:03,320 --> 00:17:05,720
LOOKING AT THE DATA, WE ACTUALLY

438
00:17:05,720 --> 00:17:07,880
FOUND SEX DIFFERENCES IN

439
00:17:07,880 --> 00:17:10,680
COGNITIVE ABILITIES BETWEEN THE

440
00:17:10,680 --> 00:17:12,360
CHILDREN IN THE WAY THAT THEY

441
00:17:12,360 --> 00:17:16,440
ACTUALLY -- THE BOYS, WITH THE

442
00:17:16,440 --> 00:17:17,840
MUTATION, THEY HAVE DECREASED

443
00:17:17,840 --> 00:17:19,160
WORKING MEMORIES COMPARED TO THE

444
00:17:19,160 --> 00:17:20,760
GIRLS WITH THE MUTATION AND I

445
00:17:20,760 --> 00:17:24,440
KNOW IT'S COMPARED TO THE

446
00:17:24,440 --> 00:17:24,880
MUTATION.

447
00:17:24,880 --> 00:17:27,560
WE PRETTY MUCH SUGGEST SEX IS A

448
00:17:27,560 --> 00:17:29,880
GENETIC RISK IN THESE EARLY LIFE

449
00:17:29,880 --> 00:17:33,360
COMMUNITY PERFORMANCE AND FOR ME

450
00:17:33,360 --> 00:17:34,880
IT'S VERY INTERESTING AND IT'S

451
00:17:34,880 --> 00:17:35,800
TELLING US THERE'S SOMETHING IN

452
00:17:35,800 --> 00:17:38,160
THE DEVELOPMENT THAT NEEDS TO BE

453
00:17:38,160 --> 00:17:40,600
FURTHER EXPLORED AND MORE THAN

454
00:17:40,600 --> 00:17:44,200
THAT, THIS INCREASED RISK OF

455
00:17:44,200 --> 00:17:45,760
FUTURE COGNITIVE ABILITY AND

456
00:17:45,760 --> 00:17:47,200
ESPECIALLY THE ONES IN THE BOYS,

457
00:17:47,200 --> 00:17:50,240
MAY HAVE IMPORTANT IMPLICATIONS

458
00:17:50,240 --> 00:17:51,600
FOR THESE CHILDREN EVEN WHEN WE

459
00:17:51,600 --> 00:17:53,840
ARE THINKING ABOUT LEARNING AND

460
00:17:53,840 --> 00:17:55,680
ACHIEVEMENT AND EVEN IN THE

461
00:17:55,680 --> 00:17:57,640
FUTURE MAY BE RELATED WITH THE

462
00:17:57,640 --> 00:18:08,120
SEX DIFFERENCES THAT ARE SEEN.

463
00:18:19,760 --> 00:18:22,320
>> WE DIDN'T HAVE TAU
PATHOLOGY

464
00:18:22,320 --> 00:18:24,800
AND IN COLOMBIA WE DIDN'T HAVE

465
00:18:24,800 --> 00:18:25,960
THAT TECHNOLOGY AND IT'S

466
00:18:25,960 --> 00:18:27,600
SOMETHING THAT I WAS MISSING

467
00:18:27,600 --> 00:18:29,880
LIKE THE SAME WE HAVE HERE AND

468
00:18:29,880 --> 00:18:32,640
WE HAVE CSS AND WE HAVE MRI BUT

469
00:18:32,640 --> 00:18:36,480
WE DON'T HAVE A PET SO FOR THIS

470
00:18:36,480 --> 00:18:37,880
I THOUGHT IT WAS VERY IMPORTANT

471
00:18:37,880 --> 00:18:39,480
TO ACTUALLY HAVE THE PIECE OF

472
00:18:39,480 --> 00:18:41,920
THE PUZZLE TO UNDERSTAND HOW THE

473
00:18:41,920 --> 00:18:44,960
TAU PATHOLOGY IN RELATION TO

474
00:18:44,960 --> 00:18:47,160
PATH OLE GOUGH FATE IN THE

475
00:18:47,160 --> 00:18:50,760
TRAJECTORY OF THE DISEASE SO IN

476
00:18:50,760 --> 00:18:54,520
2014, Dr. ROSE MENTIONED THIS

477
00:18:54,520 --> 00:18:56,560
AT BEGINNING, I APPLIED AND

478
00:18:56,560 --> 00:18:59,000
RECEIVED ONE OF THE DP5 GRANTS

479
00:18:59,000 --> 00:19:01,760
AND AS PART OF THE DP5, ACTUALLY

480
00:19:01,760 --> 00:19:03,560
PROPOSE TO BRING THE COLUMBIANS

481
00:19:03,560 --> 00:19:06,440
TO BOSTON AS PART OF WHAT I

482
00:19:06,440 --> 00:19:10,240
CALLED COLBOS AND IT'S

483
00:19:10,240 --> 00:19:11,480
COLOMBIA-BOSTON AND I WAS

484
00:19:11,480 --> 00:19:13,560
BROUGHT INTO BOSTON TO HAVE THE

485
00:19:13,560 --> 00:19:14,600
NEUROIMAGING DONE IT WAS NOT

486
00:19:14,600 --> 00:19:15,920
AVAILABLE IN COLOMBIA AND TRYING

487
00:19:15,920 --> 00:19:17,720
TO ANSWER THE QUESTION, WHAT

488
00:19:17,720 --> 00:19:24,720
HAPPENED WITH TAU PATH  PATHOLON

489
00:19:24,720 --> 00:19:26,560
THE BRAIN AND OTHER BIOMARKERS.

490
00:19:26,560 --> 00:19:31,600
WHAT WE HAVE LEARNED FROM THE

491
00:19:31,600 --> 00:19:34,680
COLBOS WE HAVE 81 INDIVIDUALS

492
00:19:34,680 --> 00:19:37,080
THAT CAME FOR BASELINE

493
00:19:37,080 --> 00:19:39,280
EXAMINATIONS AND SO WE PUT IN

494
00:19:39,280 --> 00:19:41,720
THE FIRST REPORT THAT THE

495
00:19:41,720 --> 00:19:46,840
CARRIERS ACTUALLY HAVE AMELO

496
00:19:46,840 --> 00:19:52,240
POSITIVITY AS EARLY AS THEY ARE

497
00:19:52,240 --> 00:19:53,200
28-YEARS-OLD AND WE ALSO LEARNED

498
00:19:53,200 --> 00:19:55,160
THAT THEY HAVE INCREASED TAU

499
00:19:55,160 --> 00:19:56,960
PATHOLOGY COMPARED TO THE NON

500
00:19:56,960 --> 00:19:58,800
CARRIERS IN THE LATE 30s AND

501
00:19:58,800 --> 00:20:02,680
NOW WE KNOW THAT IT'S AS EARLY

502
00:20:02,680 --> 00:20:04,360
AS THEY ARE 36, A FEW YEARS

503
00:20:04,360 --> 00:20:07,560
BEFORE THE CLINICAL ONSET AND WE

504
00:20:07,560 --> 00:20:09,120
ALSO NOW KNOW THE ACCUMULATION

505
00:20:09,120 --> 00:20:13,160
OR TAU PATHOLOGY BEGINS AND THE

506
00:20:13,160 --> 00:20:15,160
CORTEX AND IT'S EXPRESSED FROM

507
00:20:15,160 --> 00:20:17,680
THE CORTEX TO OTHER REGIONS.

508
00:20:17,680 --> 00:20:19,760
WE ALSO LEARNED THAT INCREASED

509
00:20:19,760 --> 00:20:21,720
LAYERS OF TAU WOULD ONLY SEEN IN

510
00:20:21,720 --> 00:20:26,640
THE SETTING OF STUB TAN SHALL

511
00:20:26,640 --> 00:20:29,120
OPPOSITION AND ALL INDIVIDUALS

512
00:20:29,120 --> 00:20:29,720
THAT ACTUAL WILL HE HAVE HIGH

513
00:20:29,720 --> 00:20:35,880
LAYERS OF TAU ALREADY HAD HIGH

514
00:20:35,880 --> 00:20:42,960
LEVELS OF AMYLOID AND IT WAS

515
00:20:42,960 --> 00:20:44,840
CORRALLATED WITH DECLINE AND WE

516
00:20:44,840 --> 00:20:51,400
KNOW AMYLOID WITH DECLINE THAT

517
00:20:51,400 --> 00:20:53,240
AMYLOID AND THE OTHER THINGS IN

518
00:20:53,240 --> 00:20:55,080
THE PICTURE, WHEN THEY LOOK BY

519
00:20:55,080 --> 00:20:57,240
COGNITIVE IMPAIRMENT, TAU

520
00:20:57,240 --> 00:21:01,400
PATHOLOGY IS SPREAD IN THE NEO

521
00:21:01,400 --> 00:21:03,360
CORTEX IS (INAUDIBLE).

522
00:21:03,360 --> 00:21:05,360
JUST RECENTLY AND THIS IS

523
00:21:05,360 --> 00:21:09,560
SOMETHING THAT MY COLLEAGUES

524
00:21:09,560 --> 00:21:11,280
WERE LEADING THIS EFFORT SO WE

525
00:21:11,280 --> 00:21:13,760
STARTED GOING BACK TO THE

526
00:21:13,760 --> 00:21:14,840
CONNECTIVITY, WHICH I'M STILL

527
00:21:14,840 --> 00:21:17,640
VERY INTO THE COGNITIVE TEE SO

528
00:21:17,640 --> 00:21:19,560
WE TRIED TO HAVE THE ASSOCIATION

529
00:21:19,560 --> 00:21:22,840
WITH TAU PATHOLOGY AND BRAIN

530
00:21:22,840 --> 00:21:23,440
CONNECTIVITY AND USING THE

531
00:21:23,440 --> 00:21:26,200
APPROACH OF USING SEEING IF

532
00:21:26,200 --> 00:21:29,040
THERE WAS ANY ASSOCIATIONS OF

533
00:21:29,040 --> 00:21:30,120
TAU PATHOLOGY AND THE FUNCTION

534
00:21:30,120 --> 00:21:32,720
OF SEGREGATION AND INTEGRATION

535
00:21:32,720 --> 00:21:37,160
IN THE BRAIN NETWORKS AND WE

536
00:21:37,160 --> 00:21:40,640
ACTUALLY FOUND THE MUTATION

537
00:21:40,640 --> 00:21:41,880
CARRIERS HAVE ASKING ROW GAYS

538
00:21:41,880 --> 00:21:45,400
AND INTEGRATION IN THE FORMAL

539
00:21:45,400 --> 00:21:47,040
NETWORKS AS YOU SEE HERE AND WE

540
00:21:47,040 --> 00:21:48,640
TOOK OUT THE ASSOCIATION WITH

541
00:21:48,640 --> 00:21:51,160
TAU WE FOUND THE GREATER TAU

542
00:21:51,160 --> 00:21:53,440
PATHOLOGY WAS ACTUALLY

543
00:21:53,440 --> 00:21:54,680
ASSOCIATED WITH LOWER

544
00:21:54,680 --> 00:21:57,680
SEGREGATION AND INTERNET GRA

545
00:21:57,680 --> 00:22:00,200
TIVE AND I'M SORRY.

546
00:22:00,200 --> 00:22:02,960
PRETTY MUCH HERE IN THIS FIRST

547
00:22:02,960 --> 00:22:05,640
REPORT WE'RE SHOW THAT EVEN

548
00:22:05,640 --> 00:22:07,680
THOSE LEVELS OF TAU PATHOLOGY,

549
00:22:07,680 --> 00:22:12,680
WHICH IN THE SAMPLE, THEY'RE

550
00:22:12,680 --> 00:22:14,800
VERY INSIM LEVELS TO THEY'RE

551
00:22:14,800 --> 00:22:16,280
STARTING IN THE BRAINS AND THOSE

552
00:22:16,280 --> 00:22:18,200
LEVELS ARE ALREADY IN PART IN

553
00:22:18,200 --> 00:22:21,640
THE BRAIN FUNCTION ORGANIZATION

554
00:22:21,640 --> 00:22:22,840
SEVERAL YEARS BEFORE THEY HAVE

555
00:22:22,840 --> 00:22:23,160
IMPAIRMENT.

556
00:22:23,160 --> 00:22:28,360
ALL OF THIS IS I DIDN'T SHOW

557
00:22:28,360 --> 00:22:31,280
THIS DESCRIPTION BUT THEY

558
00:22:31,280 --> 00:22:34,920
IMPAIRED AND WE ONLY HAVE SEVEN

559
00:22:34,920 --> 00:22:42,240
WITH COGNITIVE IMPAIRMENT.

560
00:22:42,240 --> 00:22:44,480
WE STARTED AND THE BIOMARKER

561
00:22:44,480 --> 00:22:46,480
STARTED AND AS PART OF THE

562
00:22:46,480 --> 00:22:48,600
LONGITUDINAL MARKER ASIDE, WE

563
00:22:48,600 --> 00:22:50,760
INVITED INDIVIDUALS TO COME BACK

564
00:22:50,760 --> 00:22:53,840
FOR FOLLOW-UP, EXAMINATIONS AND

565
00:22:53,840 --> 00:22:57,240
THEY WERE COMING BACK AFTER 18

566
00:22:57,240 --> 00:22:58,520
TO 24 HOURS AND THIS PART WAS

567
00:22:58,520 --> 00:23:01,680
RUNNING VERY SMOOTHLY UNTIL I'M

568
00:23:01,680 --> 00:23:04,320
GOING TO SHOW YOU THE ONES THAT

569
00:23:04,320 --> 00:23:08,480
WE COLLECTED BEFORE AND SO FAR

570
00:23:08,480 --> 00:23:09,520
WE HAVE 35 THAT HAVE BEEN ABLE

571
00:23:09,520 --> 00:23:15,760
TO COME BACK FOR THE THREE TIMES

572
00:23:15,760 --> 00:23:18,240
AND AS PART OF THE FOLLOW-UP

573
00:23:18,240 --> 00:23:19,200
THIS IS SOMETHING THAT WAS

574
00:23:19,200 --> 00:23:21,480
SLOWED WE FOUND THAT CARRIERS

575
00:23:21,480 --> 00:23:23,760
COMPARED TO THE NON CARRIERS

576
00:23:23,760 --> 00:23:26,320
HAVE GREATER TAU PATHOLOGY AS

577
00:23:26,320 --> 00:23:32,720
YOU CAN SEE HERE AND IT WAS VERY

578
00:23:32,720 --> 00:23:33,760
INTERESTING AND I FOUND VERY

579
00:23:33,760 --> 00:23:35,880
INTERESTING AND IT'S SOMETHING

580
00:23:35,880 --> 00:23:38,160
WITH MORE WE HAVE BEEN ABLE TO

581
00:23:38,160 --> 00:23:39,960
CONFIRM HERE WE HAVE THE

582
00:23:39,960 --> 00:23:42,320
CARRIERS AND THEY'RE IN BLUE AND

583
00:23:42,320 --> 00:23:44,840
THE FEW THAT WE HAVE THERE FOR

584
00:23:44,840 --> 00:23:45,880
IMPAIR AND THE CONTROLS AND YOU

585
00:23:45,880 --> 00:23:50,120
CAN ACTUALLY SEE THAT THE

586
00:23:50,120 --> 00:23:52,680
UNIMPAIRED ACCUMULATION OR AM

587
00:23:52,680 --> 00:23:54,080
LLOYD APPEARS TO BE A STEADY

588
00:23:54,080 --> 00:23:57,040
PROCESS AND BEGINNING AS EARLY

589
00:23:57,040 --> 00:23:58,800
AS 20 YEARS PRIOR TO THE

590
00:23:58,800 --> 00:24:00,960
DEMENTIA ONSET AND HERE IS

591
00:24:00,960 --> 00:24:07,080
AMYLOID AND THIS IS H AND YOU

592
00:24:07,080 --> 00:24:08,480
CAN SHOW TAU COMPARED TO ACE YOU

593
00:24:08,480 --> 00:24:10,520
CAN SEE IN CONTRAST, TAU

594
00:24:10,520 --> 00:24:13,720
PATHOLOGY IS VERY RAPID AND

595
00:24:13,720 --> 00:24:15,560
WIDESPREAD IN THE TAU AND YOU

596
00:24:15,560 --> 00:24:17,320
CAN SEE IT ACTUALLY, NOTHING

597
00:24:17,320 --> 00:24:18,800
MUCH HAPPENS IN THE EARLY 30s

598
00:24:18,800 --> 00:24:20,320
BUT AS SOON AS THEY GET CLOSER

599
00:24:20,320 --> 00:24:23,520
YOU CAN SEE THESE RAPID INCREASE

600
00:24:23,520 --> 00:24:26,040
OR TAU AND NOW THAT WE HAVE MORE

601
00:24:26,040 --> 00:24:28,800
AND THE PATTERN IS VERY SIMILAR

602
00:24:28,800 --> 00:24:29,040
AS WELL.

603
00:24:29,040 --> 00:24:30,560
TO TAU AND AMYLOID CHANGES THE

604
00:24:30,560 --> 00:24:34,000
MEASURES ARE VERY CORRELATED AND

605
00:24:34,000 --> 00:24:35,240
TAU BASELINE AND THE CHANGES ARE

606
00:24:35,240 --> 00:24:38,040
ALSO LINKED TO MEMORY DECLINE

607
00:24:38,040 --> 00:24:40,080
AND MORE LINKED TO MEMORY

608
00:24:40,080 --> 00:24:43,040
DECLINE THAN AMYLOID.

609
00:24:43,040 --> 00:24:46,880
WITH ALL THIS DATA YOU CAN SEE

610
00:24:46,880 --> 00:24:48,960
WE HAVE TRIED TO MAKE A

611
00:24:48,960 --> 00:24:53,120
DIFFERENCE WITH DIFFERENT

612
00:24:53,120 --> 00:24:54,720
QUESTIONS AND ALL ARE USED TO

613
00:24:54,720 --> 00:24:55,320
IMPROVE BIO MARKERS AND

614
00:24:55,320 --> 00:24:56,920
UNDERSTAND AND PROTECT AND RAISE

615
00:24:56,920 --> 00:24:59,080
FACTORS FOR THOSE RELATED

616
00:24:59,080 --> 00:25:02,480
COMMUNITY DELINE AND DEMENTIA

617
00:25:02,480 --> 00:25:07,000
USING THIS DISEASE AND WE ARE IN

618
00:25:07,000 --> 00:25:08,520
THE DEX SISS IN THIS FOR

619
00:25:08,520 --> 00:25:11,400
INSTANCE AND ALSO UNDERSTANDING

620
00:25:11,400 --> 00:25:14,880
THE LEAD AND PHYSICAL ACTIVITIES

621
00:25:14,880 --> 00:25:19,480
AND CHRONIC STRESS AND AND THE

622
00:25:19,480 --> 00:25:21,720
SIGN THAT THE FACTORS AND OF

623
00:25:21,720 --> 00:25:24,160
COURSE OTHER FACTORS AS WELL AND

624
00:25:24,160 --> 00:25:26,240
WHY HAVE TIME TO GO THROUGH ALL

625
00:25:26,240 --> 00:25:28,160
THIS SLIDES BUT I'LL HIGHLIGHT A

626
00:25:28,160 --> 00:25:30,920
FEW OF THEM JUST FOR YOU TO GIVE

627
00:25:30,920 --> 00:25:32,520
ATTENTION TO WHAT WE DO TO I'M

628
00:25:32,520 --> 00:25:34,400
GOING TO START WITH SOME OF THE

629
00:25:34,400 --> 00:25:35,600
APPLICATIONS OF THE WORK THAT WE

630
00:25:35,600 --> 00:25:37,200
HAVE BEEN DOING AND STARTING

631
00:25:37,200 --> 00:25:41,000
WITH EARLY DIAGNOSIS.

632
00:25:41,000 --> 00:25:43,080
OF COGNITIVE DECLINE AND

633
00:25:43,080 --> 00:25:47,440
DEMENTIA AND EVERYTHING WE DO

634
00:25:47,440 --> 00:25:48,840
WITH THE COLUMBIAN KINDRED WE DO

635
00:25:48,840 --> 00:25:51,080
IN SPANISH AND WE VALIDATE AND

636
00:25:51,080 --> 00:25:52,560
DEVELOP SOME OF THE MEASURES FOR

637
00:25:52,560 --> 00:25:54,280
A TESTING IN SPANISH SPEAKERS

638
00:25:54,280 --> 00:25:56,320
AND THIS IS ONE EXAMPLE SO THE

639
00:25:56,320 --> 00:25:57,440
FIRST THING ASSOCIATED WITH

640
00:25:57,440 --> 00:26:01,560
MEMBER ROW EXERCISE FACE NAME,

641
00:26:01,560 --> 00:26:03,240
WAS ONE THAT WAS ACTUALLY

642
00:26:03,240 --> 00:26:05,880
SHOWING TO BE SENSITIVE TO

643
00:26:05,880 --> 00:26:07,360
CLINICAL ALZHEIMER'S DISEASE AND

644
00:26:07,360 --> 00:26:09,880
WE ACTUALLY CREATED THE LATINO

645
00:26:09,880 --> 00:26:12,280
AMERICAN VERSION VALIDATED

646
00:26:12,280 --> 00:26:13,840
VERSION IN THE COLOMBIA SAMPLE

647
00:26:13,840 --> 00:26:16,920
AND CREATING NORMS FOR CLINICAL

648
00:26:16,920 --> 00:26:17,600
USE.

649
00:26:17,600 --> 00:26:20,080
THERE IS THIS PAPER AND FOR

650
00:26:20,080 --> 00:26:21,680
CLINICAL USE WE ACTUALLY USE IT

651
00:26:21,680 --> 00:26:25,600
IN COLBOS TO TEST IT INTACT

652
00:26:25,600 --> 00:26:26,520
INDIVIDUALS TO SEE IF THE

653
00:26:26,520 --> 00:26:30,240
MEASURE WAS ACTUALLY ABLE TO

654
00:26:30,240 --> 00:26:32,240
DETECT A CARRIER FROM

655
00:26:32,240 --> 00:26:34,480
NON-CARRIERS AND WHETHER IT WAS

656
00:26:34,480 --> 00:26:37,160
CORRELATED WITH TAU POTHOLOGY.

657
00:26:37,160 --> 00:26:38,280
THIS IS SOME OF THE WORK ONE OF

658
00:26:38,280 --> 00:26:40,800
MY DOCTORS WAS ACTUALLY LEADING.

659
00:26:40,800 --> 00:26:43,280
THIS IS HOW THE TASK LOOKS.

660
00:26:43,280 --> 00:26:46,600
THE TASK IS AVAILABLE AS PART OF

661
00:26:46,600 --> 00:26:50,880
THE NIH TOOLBOX SO WE HAVE THE

662
00:26:50,880 --> 00:26:54,120
LEARN PHASE AND THEY HAD TO

663
00:26:54,120 --> 00:26:54,760
IDENTIFY AND RECOGNIZE THE FACE

664
00:26:54,760 --> 00:26:57,760
AND THE LETTER AND THE NAME.

665
00:26:57,760 --> 00:27:00,800
SO WHAT WE ACTUALLY FOUND WITH

666
00:27:00,800 --> 00:27:03,800
THE COLBOS DATA IT ENCLOUDS ONLY

667
00:27:03,800 --> 00:27:06,120
ONE THAT ARE CONSIDERED

668
00:27:06,120 --> 00:27:07,280
COGNITIVELY INTACT.

669
00:27:07,280 --> 00:27:08,320
THEY DON'T HAVE CONCERNS OF

670
00:27:08,320 --> 00:27:09,120
MEMBER ROW.

671
00:27:09,120 --> 00:27:10,960
AS CLEAN AS IT GETS.

672
00:27:10,960 --> 00:27:13,760
AND WE ACTUALLY WERE ABLE TO USE

673
00:27:13,760 --> 00:27:16,440
THIS TEST TO SHOW THAT ONLY A

674
00:27:16,440 --> 00:27:22,400
PERFORMANCE IN THE TASK, AS ABLE

675
00:27:22,400 --> 00:27:25,680
TO DISTINGUISH CARRIERS FROM NON

676
00:27:25,680 --> 00:27:26,000
CARRIERS.

677
00:27:26,000 --> 00:27:27,640
THEY DEFINE THE CARRIERS FROM

678
00:27:27,640 --> 00:27:29,320
NON CARRIERS EVEN WITHIN THE

679
00:27:29,320 --> 00:27:31,560
NORMAL RANGE OF PERFORMANCE.

680
00:27:31,560 --> 00:27:32,720
WE THEN LOOKED AT THE

681
00:27:32,720 --> 00:27:34,400
CORRELATIONS WITH PATHOLOGY AND

682
00:27:34,400 --> 00:27:37,000
HERE AND SHOW THE PERFORMANCE

683
00:27:37,000 --> 00:27:38,920
AND IMMUNO PATHOLOGY AND THE

684
00:27:38,920 --> 00:27:40,480
WORST PERFORMANCE IN THE TEST

685
00:27:40,480 --> 00:27:42,800
WAS CORRELATED WITH GREATER

686
00:27:42,800 --> 00:27:44,440
AMYLOID AND THE SAME IN

687
00:27:44,440 --> 00:27:46,360
INDIVIDUALS WITH NO AND

688
00:27:46,360 --> 00:27:47,880
COGNITIVE CONCERNS OR COGNITIVE

689
00:27:47,880 --> 00:27:50,640
DECLINE AND THEN WE DID THE SAME

690
00:27:50,640 --> 00:27:53,600
WITH INTER RYAN A AND FIRST WAS

691
00:27:53,600 --> 00:27:56,120
ASSOCIATED AND WE WERE WITH

692
00:27:56,120 --> 00:27:59,320
GREATER LEVELS OF PATHOLOGY AS

693
00:27:59,320 --> 00:28:01,400
WELL AND THEN AS THE ANALYSIS WE

694
00:28:01,400 --> 00:28:04,200
USED THE ASSOCIATIONS WITH

695
00:28:04,200 --> 00:28:07,720
PERFORMANCE AND THE TAU

696
00:28:07,720 --> 00:28:09,880
PATHOLOGY HERE AND AMYLOID HERE

697
00:28:09,880 --> 00:28:11,560
AND THE REGIONS OF THE BRAIN

698
00:28:11,560 --> 00:28:15,480
WERE MORE WITH PERFORMANCE AND

699
00:28:15,480 --> 00:28:16,600
IN THE TAU IN PARTICULAR AND

700
00:28:16,600 --> 00:28:18,400
THEN THE ONES WE KNOW THAT ARE

701
00:28:18,400 --> 00:28:19,920
SENSITIVE TO EARLY ACCUMULATION

702
00:28:19,920 --> 00:28:21,400
OF PATHOLOGY AS WELL.

703
00:28:21,400 --> 00:28:24,920
ONCE AGAIN, IN INDIVIDUALS WITH

704
00:28:24,920 --> 00:28:27,240
NO COGNITIVE SYMPTOMS SO IT'S A

705
00:28:27,240 --> 00:28:29,800
PROMISING TASK AND WE CONTINUE

706
00:28:29,800 --> 00:28:38,440
TO USE IT IN THE STUDY AS WELL.

707
00:28:38,440 --> 00:28:42,360
WITH TO THE REMOTE TESTING, WE

708
00:28:42,360 --> 00:28:44,880
DID TOO SO I ACTUALLY CREATED

709
00:28:44,880 --> 00:28:47,480
THE COVID REMOTE AND I WAS

710
00:28:47,480 --> 00:28:50,200
PRETTY MUCH A STUDY IN COLOMBIA.

711
00:28:50,200 --> 00:28:53,440
WHEN WE RECRUITED A COHORT OR

712
00:28:53,440 --> 00:28:56,000
INDIVIDUALS AND PRETTY MUCH WERE

713
00:28:56,000 --> 00:29:04,720
GOING TO AND UNDER WIND A REMOTE

714
00:29:04,720 --> 00:29:05,840
TESTING AND BLOOD TESTING EITHER

715
00:29:05,840 --> 00:29:09,400
IN THE COMPUTER OR IN THE

716
00:29:09,400 --> 00:29:10,640
SMARTPHONE SO WE USED THE

717
00:29:10,640 --> 00:29:12,280
OPPORTUNITY TO ACTUALLY VALIDATE

718
00:29:12,280 --> 00:29:16,040
SOME OF THE MEASURES THAT WERE

719
00:29:16,040 --> 00:29:18,120
DESIGNED FOR REMOTE TESTING AND

720
00:29:18,120 --> 00:29:19,920
WE HAD SO FAR FOUR MEASURES THAT

721
00:29:19,920 --> 00:29:21,640
ARE NOVEL MEASURES AT A

722
00:29:21,640 --> 00:29:24,960
DIFFERENT STAGES OR PILOTING AND

723
00:29:24,960 --> 00:29:27,920
I'M GOING TO SHARE ONE THAT IS

724
00:29:27,920 --> 00:29:29,160
MORE ADVANCED AND THE MEASURES

725
00:29:29,160 --> 00:29:32,920
THAT WE HAVE IN DIFFERENT STEPS

726
00:29:32,920 --> 00:29:35,840
AND THEY ARE MULTI CULTURAL,

727
00:29:35,840 --> 00:29:36,640
MULTI LINGUAL SO RIGHT NOW WE

728
00:29:36,640 --> 00:29:39,800
HAVE IN ENGLISH, SPANISH AND

729
00:29:39,800 --> 00:29:41,960
KOREAN AND WE'RE DEVELOPING ONE

730
00:29:41,960 --> 00:29:42,680
IN PORTUGUESE AS WELL.

731
00:29:42,680 --> 00:29:45,920
SO THE IDEA IS TO HAVE THIS

732
00:29:45,920 --> 00:29:47,080
AVAILABLE IN THE FUTURE FOR

733
00:29:47,080 --> 00:29:49,080
ANYONE THAT WANTS ACCESS TO

734
00:29:49,080 --> 00:29:49,440
THESE MEASURES.

735
00:29:49,440 --> 00:29:52,760
SO I WANTED TO SHARE WITH YOU AS

736
00:29:52,760 --> 00:29:56,120
AN EXAMPLE IS MEMORY RELATED OR

737
00:29:56,120 --> 00:30:02,920
JUST DEMONSTRATED AND HERE IS

738
00:30:02,920 --> 00:30:03,600
ONE MY PH.D STUDENT WAS LEADING

739
00:30:03,600 --> 00:30:06,760
THIS EFFORT AND WE HAVE OBJECTS

740
00:30:06,760 --> 00:30:09,200
RELATED VERSUS THESE RELATED AND

741
00:30:09,200 --> 00:30:11,040
THEY HAVE TO LEARN THESE BASED

742
00:30:11,040 --> 00:30:13,920
ON THE DELAYED EXAMPLE OF THE

743
00:30:13,920 --> 00:30:16,520
TEST AND THEY HAVE TO JUST SAY

744
00:30:16,520 --> 00:30:20,480
THEY MATCH OR NO MATCH AND AFTER

745
00:30:20,480 --> 00:30:23,120
A FEW SECONDS DELAY AND WHAT WE

746
00:30:23,120 --> 00:30:27,560
FOUND IS THIS IS INCLUDING ONLY

747
00:30:27,560 --> 00:30:29,680
COMPLETED THE TASK IN THE

748
00:30:29,680 --> 00:30:30,680
COMPUTER SO THEY WERE GIVEN THE

749
00:30:30,680 --> 00:30:32,920
OPTION OF COMPLETING IT IN THE

750
00:30:32,920 --> 00:30:35,320
COMPUTER OR THE SMARTPHONE AND

751
00:30:35,320 --> 00:30:38,400
HERE FOR THIS ANALYSIS WE ONLY

752
00:30:38,400 --> 00:30:39,560
INCLUDED THE ONES COMPLETED IN

753
00:30:39,560 --> 00:30:42,000
THE COMPUTER SO WE HAVE 35 THAT

754
00:30:42,000 --> 00:30:47,000
WERE CARRIERS AND 23 THAT WERE

755
00:30:47,000 --> 00:30:50,360
NON CARRIERS AND FIVE THAT WERE

756
00:30:50,360 --> 00:30:52,280
MCI AND WHAT WE'RE SEEING WITH

757
00:30:52,280 --> 00:30:55,320
THE PERFORMANCE IS THE TOTAL

758
00:30:55,320 --> 00:30:58,600
PERFORMANCE WAS THE SAME AND IT

759
00:30:58,600 --> 00:31:01,760
WAS DIFFERENT EVEN WITHIN THE

760
00:31:01,760 --> 00:31:03,160
NORMAL RANGE AND ALSO BETWEEN

761
00:31:03,160 --> 00:31:06,360
THE TWO CONDITIONS THE RELATED

762
00:31:06,360 --> 00:31:07,880
WERE THOSE THAT WERE

763
00:31:07,880 --> 00:31:08,680
CONTRIBUTING TO THE DIFFERENCE

764
00:31:08,680 --> 00:31:10,600
BETWEEN THE CARRIERS AND THE NON

765
00:31:10,600 --> 00:31:11,000
CARRIERS.

766
00:31:11,000 --> 00:31:13,000
AND WE LOOK AT THE TWO

767
00:31:13,000 --> 00:31:14,480
CONDITIONS THAT WERE FOUR ITEMS

768
00:31:14,480 --> 00:31:17,320
VERSUS SIX ITEMS, THE ONLY FOUR

769
00:31:17,320 --> 00:31:19,320
ITEMS FOR INSTANCE WAS THE ONE

770
00:31:19,320 --> 00:31:22,360
THAT WAS A DISTINGUISHED IN THE

771
00:31:22,360 --> 00:31:24,880
CARRIERS COMPARED TO UNIMPAIRED

772
00:31:24,880 --> 00:31:27,080
VERSUS THE KNOWN CARRIERS, THE

773
00:31:27,080 --> 00:31:29,600
MCI THEY PERFORMED LOWER IN

774
00:31:29,600 --> 00:31:30,120
EVERYTHING.

775
00:31:30,120 --> 00:31:32,640
BUT THIS IS JUST AN EXAMPLE TO

776
00:31:32,640 --> 00:31:34,920
SHOW YOU THAT THE OPPORTUNITY

777
00:31:34,920 --> 00:31:37,800
FOR DESIGNING MEASURES THAT CAN

778
00:31:37,800 --> 00:31:40,200
ACTUALLY DETECTOR BE MORE

779
00:31:40,200 --> 00:31:46,720
SENSITIVE FOR A CLINICAL AND

780
00:31:46,720 --> 00:31:47,920
SUBSIDAL CHANGES TO TAKE

781
00:31:47,920 --> 00:31:49,560
INDIVIDUALS THAT ARE GOING TO BE

782
00:31:49,560 --> 00:31:51,640
DEVELOPING COGNITIVE DECLINE IN

783
00:31:51,640 --> 00:31:54,280
THE FUTURE AND INSTEAD OF USING

784
00:31:54,280 --> 00:31:56,680
THE SAME MEASURES THAT WE HAVE

785
00:31:56,680 --> 00:31:59,040
TRADITIONALLY USED TO IDENTIFY

786
00:31:59,040 --> 00:32:02,480
WITH MICHAEL AND DEMENTIA.

787
00:32:02,480 --> 00:32:03,960
SO THE OTHER POINT I WANTED TO

788
00:32:03,960 --> 00:32:05,520
MENTION HERE IS THE SAME IN THIS

789
00:32:05,520 --> 00:32:08,120
PART OF THESE EARLY DETECTION,

790
00:32:08,120 --> 00:32:11,760
AS MANY IN THE FIELDS SO WE ALSO

791
00:32:11,760 --> 00:32:14,480
HAVE TAKEN A LOOK AT BLOOD

792
00:32:14,480 --> 00:32:15,600
MARKERS AND THIS IS SOMETHING

793
00:32:15,600 --> 00:32:19,400
THAT IN THE PAST, LIKE THEY HAVE

794
00:32:19,400 --> 00:32:21,040
COLLECTED BLOOD SAMPLES IN

795
00:32:21,040 --> 00:32:22,040
SEVERAL INDIVIDUALS SO WE

796
00:32:22,040 --> 00:32:25,680
STARTED LOOKING AT DATA

797
00:32:25,680 --> 00:32:28,400
COLLECTED IN THE KINDRED SO IF

798
00:32:28,400 --> 00:32:29,800
THE FIRST TWO PAPERS WE HAVE

799
00:32:29,800 --> 00:32:34,120
THAT WE PUBLISHED TWO YEARS AGO

800
00:32:34,120 --> 00:32:35,880
NOW, WE LOOK IN THE FIELD AND

801
00:32:35,880 --> 00:32:37,520
ONE THAT ARE MARKERS IN THE

802
00:32:37,520 --> 00:32:41,200
NEWER GENERATION AND ALSO THE P

803
00:32:41,200 --> 00:32:43,760
TAU TO 17 IS ONE OF THE MARKERS

804
00:32:43,760 --> 00:32:50,200
SO YEAH, OR P TAU AND IF THE

805
00:32:50,200 --> 00:32:53,400
FIRST AND OR 2,000 INDIVIDUALS,

806
00:32:53,400 --> 00:32:55,840
2,000 SAMPLES FROM THE KINDRED

807
00:32:55,840 --> 00:32:59,400
AND WE SHOWED IS THAT THE MARKER

808
00:32:59,400 --> 00:33:01,640
WAS ABLE TO DISTINGUISHED

809
00:33:01,640 --> 00:33:03,480
CARRIERS BY THE AGE OF 20 AND IT

810
00:33:03,480 --> 00:33:06,080
WAS TRUE FOR THE P TAU SO THEY

811
00:33:06,080 --> 00:33:07,080
DISTINGUISHED CARRIERS AND NO

812
00:33:07,080 --> 00:33:09,240
CARRIERS LIKE IN THE AGE OF 20

813
00:33:09,240 --> 00:33:11,360
AND HERE I SHOW YOU WHEN WE

814
00:33:11,360 --> 00:33:12,680
ACTUALLY PUT TOGETHER THE

815
00:33:12,680 --> 00:33:14,240
CARRIERS FROM THE NON CARRIERS,

816
00:33:14,240 --> 00:33:16,280
IT SEEMS LIKE THE P TAU WAS A

817
00:33:16,280 --> 00:33:17,560
LITTLE BIT MORE SENSITIVE FOR

818
00:33:17,560 --> 00:33:21,920
THE EARLIER CHANGES AND THAN THE

819
00:33:21,920 --> 00:33:23,640
SO DISTINGUISH EARLY TO EARLY

820
00:33:23,640 --> 00:33:26,520
THAN THE NON CARRIERS AND HAVING

821
00:33:26,520 --> 00:33:27,440
THIS OPPORTUNITY TO HAVE THIS

822
00:33:27,440 --> 00:33:32,200
DATA FROM BIOMARKERS, IT OPENS

823
00:33:32,200 --> 00:33:35,480
ALSO A WINDOW FOR A LOT OF

824
00:33:35,480 --> 00:33:37,120
OPPORTUNITIES IN TERMS OF

825
00:33:37,120 --> 00:33:40,680
INCREASING ACCESS, INDIVIDUALS,

826
00:33:40,680 --> 00:33:41,880
FOR INDIVIDUALS THAT DON'T HAVE

827
00:33:41,880 --> 00:33:44,120
ACCESS FOR INSTANCE IN THIS CASE

828
00:33:44,120 --> 00:33:46,560
TO GET TAU IMAGING OR AMYLOID

829
00:33:46,560 --> 00:33:47,640
IMAGING AND SO FAR.

830
00:33:47,640 --> 00:33:49,960
ONE OF THE OTHER QUESTIONS THAT

831
00:33:49,960 --> 00:33:52,160
WE HAVE HERE, AND IT'S SOMETHING

832
00:33:52,160 --> 00:33:53,800
THAT WE'RE SEEING A WORK IN

833
00:33:53,800 --> 00:33:55,160
PROGRESS, LITTLE IS KNOWN ABOUT

834
00:33:55,160 --> 00:33:56,400
THIS ASSOCIATION BETWEEN FOR

835
00:33:56,400 --> 00:33:58,960
INSTANCE MARKERS OF PLASMA AND

836
00:33:58,960 --> 00:34:01,080
MEASURES OF TAU AND ESPECIALLY

837
00:34:01,080 --> 00:34:02,040
WHEN YOU ARE THINKING ABOUT

838
00:34:02,040 --> 00:34:03,720
LONGER INTERVALS RIGHT IT'S

839
00:34:03,720 --> 00:34:05,320
SOMETHING WE CAN PREDICT AND USE

840
00:34:05,320 --> 00:34:06,680
ONE TO PREDICT CHANGES IN THE

841
00:34:06,680 --> 00:34:08,960
OTHER ONE WHEN IT'S A LONGER

842
00:34:08,960 --> 00:34:11,520
INTERVAL OF TIME SO SINCE WE

843
00:34:11,520 --> 00:34:15,520
HAVE SOME DATA FROM TAU

844
00:34:15,520 --> 00:34:20,080
PATHOLOGY, WE USE THE ONES THAT

845
00:34:20,080 --> 00:34:22,120
HAVE PATHOLOGY AND A LOCK AT

846
00:34:22,120 --> 00:34:25,160
ONES THAT HAVE THESE SAMPLES IN

847
00:34:25,160 --> 00:34:27,000
P TAU IN THIS PAPER THAT WE JUST

848
00:34:27,000 --> 00:34:29,080
SHOWED YOU AND AS THE QUESTION

849
00:34:29,080 --> 00:34:33,440
IS PLASMA TAU, IT PREDICTS

850
00:34:33,440 --> 00:34:34,960
LEVELS OF TAU PATHOLOGY AND

851
00:34:34,960 --> 00:34:36,480
COMMUNITY PERFORMANCE AND I'M

852
00:34:36,480 --> 00:34:38,920
GOING TO SPEND MORE DETAILS WHAT

853
00:34:38,920 --> 00:34:41,360
WE DID.

854
00:34:41,360 --> 00:34:43,640
SO THIS IS INDIVIDUALS THAT HAVE

855
00:34:43,640 --> 00:34:44,720
PLASMA TAU IN THE SLIDE I JUST

856
00:34:44,720 --> 00:34:46,800
SHOWED YOU AND THEN, ABOUT EIGHT

857
00:34:46,800 --> 00:34:55,520
YEARS LATER, THEY CAME TO AND

858
00:34:55,520 --> 00:34:57,400
THEY HAVE TAU AND WE USED THIS

859
00:34:57,400 --> 00:34:58,880
OPPORTUNITIES TO TEST IF THESE

860
00:34:58,880 --> 00:35:01,360
LEVELS PLASMA THAT THEY GET

861
00:35:01,360 --> 00:35:02,880
WHERE WE CALL PACE BASELINE

862
00:35:02,880 --> 00:35:12,280
WOULD HELP US PR PREDICT EIGHT

863
00:35:12,280 --> 00:35:13,840
YEARS LATER.

864
00:35:13,840 --> 00:35:15,760
WE HAVE 24 CARRIERS AND 20 THAT

865
00:35:15,760 --> 00:35:18,960
WHY NON CARRIERS SO THIS IS

866
00:35:18,960 --> 00:35:20,680
PRETTY MUCH THE SIDE THAT WE'RE

867
00:35:20,680 --> 00:35:21,360
DOING NOW.

868
00:35:21,360 --> 00:35:23,640
WE LOCK AT ONLY WITH 24 CARRIERS

869
00:35:23,640 --> 00:35:25,960
HOW BEAUTIFUL THIS LOOKS.

870
00:35:25,960 --> 00:35:29,080
SO, FIRST WE REPLICATE THAT

871
00:35:29,080 --> 00:35:32,080
CARRIERS ACTUALLY HAVE HIGHER

872
00:35:32,080 --> 00:35:35,000
LEVELS OF PET TAU 17 COMPARED TO

873
00:35:35,000 --> 00:35:38,240
THE PLASMA P-TAU IS CORRELATED

874
00:35:38,240 --> 00:35:40,680
WITH OLDER AGE.

875
00:35:40,680 --> 00:35:42,720
THEY LOOK AT COGNITION AND HERE

876
00:35:42,720 --> 00:35:44,640
THEY'RE ONLY LOOKING AND ONLY

877
00:35:44,640 --> 00:35:46,520
SHOWING ONE TEST BUT IT'S PRETTY

878
00:35:46,520 --> 00:35:48,240
MUCH ACROSS ALL THE DIFFERENT

879
00:35:48,240 --> 00:35:50,240
COMMUNITY MEASURES LIKE ACTUALLY

880
00:35:50,240 --> 00:35:54,160
P-TAU IS RECOGNITION ACROSS ALL

881
00:35:54,160 --> 00:35:57,520
THE DIFFERENT THAT WE HAVE AND

882
00:35:57,520 --> 00:36:00,360
ALMOST EIGHT YEARS LATER, AND

883
00:36:00,360 --> 00:36:05,880
THEN IT ACTUALLY LOCKS AT PATH

884
00:36:05,880 --> 00:36:08,760
PATHOLOGY AND THEY HAVE GREATER

885
00:36:08,760 --> 00:36:11,800
PATHOLOGY IN AMYLOID AND ALSO IN

886
00:36:11,800 --> 00:36:13,400
TAU AND HERE THEY'RE ONLY

887
00:36:13,400 --> 00:36:15,240
SHOWING THE FIRST ONE THAT WE

888
00:36:15,240 --> 00:36:17,040
SEE CHANGES BUT IT'S NOT ONLY

889
00:36:17,040 --> 00:36:22,880
ASSOCIATED WITH LEVELS OF

890
00:36:22,880 --> 00:36:27,880
ASSOCIATED WITH THE AND

891
00:36:27,880 --> 00:36:30,720
PRECENMEUS AND IN THE CARRIERS

892
00:36:30,720 --> 00:36:33,080
AND THE SAME ALMOST EIGHT YEARS

893
00:36:33,080 --> 00:36:35,240
LATER, THIS IS STILL PREDICTING

894
00:36:35,240 --> 00:36:36,400
THESE MEASURES.

895
00:36:36,400 --> 00:36:39,560
WE RUN SOME EXPLORATORY ANALYSIS

896
00:36:39,560 --> 00:36:41,040
AND WITH ALL THE CARRIERS YOU

897
00:36:41,040 --> 00:36:43,640
CAN SEE ESPECIALLY WITH TAU.

898
00:36:43,640 --> 00:36:46,640
TAU-PET THE TEMPORAL REGIONS AND

899
00:36:46,640 --> 00:36:50,360
SINCE WE ARE HIGHLY CORRELATED

900
00:36:50,360 --> 00:36:51,680
IS AND THESE ARE ALL THE

901
00:36:51,680 --> 00:36:52,840
CORRECTIONS WE USE AND WITH

902
00:36:52,840 --> 00:36:54,920
THESE CORRECTIONS WE TAKE A LOOK

903
00:36:54,920 --> 00:36:59,240
ONLY THE IMPAIRED CARRIERS THE

904
00:36:59,240 --> 00:37:02,880
LOBE REGIONS AND THE IT'S ALMOST

905
00:37:02,880 --> 00:37:06,880
STILL THERE EIGHT YEARS AFTER

906
00:37:06,880 --> 00:37:09,280
AND SO THIS IS UNBIASED BUT I

907
00:37:09,280 --> 00:37:11,680
THINK THIS IS VERY BEAUTIFUL.

908
00:37:11,680 --> 00:37:15,120
SO, BASELINE LAYERS OF PLASMA

909
00:37:15,120 --> 00:37:18,120
P-TAU IS LEVELS OF AMYLOID AND

910
00:37:18,120 --> 00:37:21,240
FUTURE MEMORY PERFORMANCE IN THE

911
00:37:21,240 --> 00:37:22,840
CARRIERS AND THESE RESULTS ARE

912
00:37:22,840 --> 00:37:24,800
VERY PRELIMINARY BECAUSE THERE'S

913
00:37:24,800 --> 00:37:27,160
SOME PRECISE IS NOT THAT BIG BUT

914
00:37:27,160 --> 00:37:32,880
THEY PROVIDE SUPPORT FOR PLASMA,

915
00:37:32,880 --> 00:37:38,640
T-TAU AND DIAGNOSTIC MARKER OR

916
00:37:38,640 --> 00:37:40,320
E280 COGNITION AND LEADING FROM

917
00:37:40,320 --> 00:37:41,960
AND TRIALS AS I WAS SAYING, A

918
00:37:41,960 --> 00:37:44,000
POSSIBILITY OF HAVING BLOOD

919
00:37:44,000 --> 00:37:46,600
BIOMARKERS TO INCREASE ACCESS TO

920
00:37:46,600 --> 00:37:48,480
EARLY DETECTION OF ALZHEIMER'S

921
00:37:48,480 --> 00:37:51,240
DISEASE OR AT LEAST TO THE ONES

922
00:37:51,240 --> 00:37:53,920
INCREASED RISK TO DEVELOP

923
00:37:53,920 --> 00:37:54,240
ALZHEIMER'S.

924
00:37:54,240 --> 00:37:56,280
AND THE LAST THING I WANTED TO

925
00:37:56,280 --> 00:37:59,480
MENTION, THE PROJECT THAT WE HAD

926
00:37:59,480 --> 00:38:01,880
CALLED EXTREME FOR THE LACK OF A

927
00:38:01,880 --> 00:38:04,040
BETTER GAME I CALLED IT EXTREME

928
00:38:04,040 --> 00:38:06,120
FOR THIS I WANTED TO GO TO

929
00:38:06,120 --> 00:38:08,240
EXTREME TO GO AFTER THE ONES

930
00:38:08,240 --> 00:38:10,920
THAT ACTUALLY REMAIN AND

931
00:38:10,920 --> 00:38:13,400
IMPAIRED AS PART OF THE KINDRED

932
00:38:13,400 --> 00:38:15,240
TO SEE IF WE CAN FIND CLOSE FOR

933
00:38:15,240 --> 00:38:16,840
PROTECTION AGAINST COGNITIVE

934
00:38:16,840 --> 00:38:18,760
DECLINE AND DEMENTIA AND THIS

935
00:38:18,760 --> 00:38:22,600
WAS LAUNCHED IN 2017 AND AS A

936
00:38:22,600 --> 00:38:26,120
REMINDER IN INDIVIDUALS FROM

937
00:38:26,120 --> 00:38:26,880
THIS KINDRED THEY USUALLY

938
00:38:26,880 --> 00:38:29,080
DEVELOP IMPAIRMENT AROUND THE

939
00:38:29,080 --> 00:38:30,480
AGE OF 44 AND DEMENTIA AROUND

940
00:38:30,480 --> 00:38:32,640
THE AGE OF 49 SO WE WERE AFTER

941
00:38:32,640 --> 00:38:37,760
 TTHE ONEST ARE OLDER THAN 60

942
00:38:37,760 --> 00:38:38,280
OR 65.

943
00:38:38,280 --> 00:38:39,640
THE FIRST CASE IS THE ONE THAT

944
00:38:39,640 --> 00:38:45,720
WE REPORTED IN 2019 AND SHE WAS

945
00:38:45,720 --> 00:38:48,960
72 WHEN SHE STARTED SHOWING

946
00:38:48,960 --> 00:38:50,960
SIGNS OF COGNITIVE DECLINE.

947
00:38:50,960 --> 00:38:53,040
ALMOST THREE DECADES AFTER THE

948
00:38:53,040 --> 00:38:55,080
EXPECTED AGE OF CLINICAL ONSET

949
00:38:55,080 --> 00:38:59,200
AND THE FAMILY BROUGHT HER TO

950
00:38:59,200 --> 00:39:02,920
THE DOCTOR IN COLOMBIA AND BY

951
00:39:02,920 --> 00:39:04,800
THE TIME SHE WAS SEEN BY HIM SO

952
00:39:04,800 --> 00:39:06,920
SHE WAS RELATIVE LOW HEALTHY AND

953
00:39:06,920 --> 00:39:11,440
THE ONLY THING THAT WAS HER

954
00:39:11,440 --> 00:39:14,080
MEDICAL HISTORY SHE HAD HIGH

955
00:39:14,080 --> 00:39:15,840
LEVELS OF CHOLESTEROL.

956
00:39:15,840 --> 00:39:17,240
NOTHING THAT WAS QUITE

957
00:39:17,240 --> 00:39:19,040
SIGNIFICANT.

958
00:39:19,040 --> 00:39:21,120
SO SHE WASN'T BROUGHT IN COLBOS

959
00:39:21,120 --> 00:39:26,600
AND SHE CAME TO IMAGING AND I'M

960
00:39:26,600 --> 00:39:28,200
GOING TO WALK YOU THROUGH THE

961
00:39:28,200 --> 00:39:34,400
IMAGING FINDINGS HERE.

962
00:39:34,400 --> 00:39:37,960
YOU ARE NOT SEEING WHAT I'M

963
00:39:37,960 --> 00:39:38,640
SEEING.

964
00:39:38,640 --> 00:39:38,840
OK.

965
00:39:38,840 --> 00:39:43,000
SO, HERE YOU CAN SEE THE AMYLOID

966
00:39:43,000 --> 00:39:44,520
PATHOLOGY AND ALL THIS TIME I

967
00:39:44,520 --> 00:39:49,840
WAS JUST CLICKING HERE.

968
00:39:49,840 --> 00:39:50,880
I APOLOGIZE.

969
00:39:50,880 --> 00:39:52,720
SO THE AMYLOID HERE THIS IS

970
00:39:52,720 --> 00:39:54,880
COMPARED TO THE TYPICAL MCI AND

971
00:39:54,880 --> 00:39:58,080
YOU CAN SEE THE LAYERS OF

972
00:39:58,080 --> 00:40:00,000
AMYLOID WERE REALLY HIGH, THE

973
00:40:00,000 --> 00:40:02,480
HIGHEST WE'VE SEEN IN ANYBODY IN

974
00:40:02,480 --> 00:40:03,440
THE KINDRED AND THE SECOND ROW

975
00:40:03,440 --> 00:40:05,880
HERE IS THE LAYERS OF TAU SO

976
00:40:05,880 --> 00:40:07,800
THIS IS COMPARED TO THE MCI AND

977
00:40:07,800 --> 00:40:10,840
YOU CAN SEE THE LEVELS OF TAU

978
00:40:10,840 --> 00:40:13,840
WERE VERY LIMIT AND JUST VERY

979
00:40:13,840 --> 00:40:15,480
LIMITED IN DEALS SO IN THE

980
00:40:15,480 --> 00:40:17,520
LOCATION AND THE TAU WAS

981
00:40:17,520 --> 00:40:19,280
ACTUALLY ACCUMULATING AND THE

982
00:40:19,280 --> 00:40:23,000
WAY TO SEE IT IT HERE AND SO

983
00:40:23,000 --> 00:40:26,240
SHE'S THE ONE IN RED AND

984
00:40:26,240 --> 00:40:27,320
EVERYTHING ELSE WE HAVE AT THAT

985
00:40:27,320 --> 00:40:30,880
POINT IN THE KINDRED, THE

986
00:40:30,880 --> 00:40:34,680
BLACK -- THE BLACK ONE IS THE M.

987
00:40:34,680 --> 00:40:39,760
>> CatherineCIAND THE
CARRIERS E

988
00:40:39,760 --> 00:40:42,080
AMYLOID HERE AND YOU HAVE TAU

989
00:40:42,080 --> 00:40:43,320
HERE SO THE RED.

990
00:40:43,320 --> 00:40:45,400
HIGH LEVELS OF AMYLOID AND

991
00:40:45,400 --> 00:40:47,320
LIMITED LEVELS OF TAU AND WE RUN

992
00:40:47,320 --> 00:40:49,000
SOME STRUCTURAL IMAGING AND THE

993
00:40:49,000 --> 00:40:51,640
SAME SHE'S THE ONE IN RED SO HER

994
00:40:51,640 --> 00:40:53,520
LEVELS OF ATROPHY WERE LIMITED

995
00:40:53,520 --> 00:40:56,600
AND WHEN WE SEE HER FIRST AND

996
00:40:56,600 --> 00:41:00,400
SHE HAD NO LAYERS OF METABOLISM

997
00:41:00,400 --> 00:41:02,360
WHEN WE SAW HER AND IT'S WHAT WE

998
00:41:02,360 --> 00:41:03,760
SAW THERE AND ALSO WHAT YOU SEE

999
00:41:03,760 --> 00:41:07,760
IN THIS PICTURE RIGHT HERE.

1000
00:41:07,760 --> 00:41:09,600
SO YES, THE IMAGING SHOWED US

1001
00:41:09,600 --> 00:41:12,680
YOU HAVE A LIMITED TAU PATHOLOGY

1002
00:41:12,680 --> 00:41:14,040
AND DESPITE HAVING REALLY HIGH

1003
00:41:14,040 --> 00:41:15,640
LEVELS OF AMYLOID AND THE OTHER

1004
00:41:15,640 --> 00:41:17,360
THING THAT WE DID IS THAT WE

1005
00:41:17,360 --> 00:41:20,040
TOOK OUT A REALLY CLOSE LOOK NO

1006
00:41:20,040 --> 00:41:21,960
THE TAU LEVELS AND THIS IS LIKE

1007
00:41:21,960 --> 00:41:26,320
A FLOOD MAP FOR HER TEMPORAL

1008
00:41:26,320 --> 00:41:28,920
LOBE CORTEX AND IT DOES THE

1009
00:41:28,920 --> 00:41:30,760
CORTEX AND CAN YOU SEE THAT SHE

1010
00:41:30,760 --> 00:41:33,600
HAS A LITTLE TAU IN THE CORTEX

1011
00:41:33,600 --> 00:41:35,080
BUT NOTHING COMPARED WHEN YOU

1012
00:41:35,080 --> 00:41:37,440
ACTUALLY LOCK AT THE C AND THE D

1013
00:41:37,440 --> 00:41:39,760
AND IT'S SOMEONE THAT IS A

1014
00:41:39,760 --> 00:41:42,800
SYMPTOMATIC FROM THE KINDRED

1015
00:41:42,800 --> 00:41:45,280
THERE'S A TED AND YOU COMPARE

1016
00:41:45,280 --> 00:41:47,640
HER WITH A CONTROLLER IT'S THE

1017
00:41:47,640 --> 00:41:48,280
SAME CHROME WE HAVE IN THE

1018
00:41:48,280 --> 00:41:51,800
PREVIOUS SLIDE AND IT WAS A

1019
00:41:51,800 --> 00:41:52,640
44--YEAR-OLD CARRIERS.

1020
00:41:52,640 --> 00:41:54,880
SO PRETTY MUCH HAD LAYERS OF TAU

1021
00:41:54,880 --> 00:41:56,880
WHERE EXTREMELY LIMITED COMPARED

1022
00:41:56,880 --> 00:42:00,040
TO ANYONE IN THE INTRIED SO WE

1023
00:42:00,040 --> 00:42:02,440
RAN SOME GENETIC ANALYSIS ON HER

1024
00:42:02,440 --> 00:42:06,120
AND FIRST WE CONFIRMED SHE WAS A

1025
00:42:06,120 --> 00:42:08,000
CARRIER AND THE MUTATION AND WE

1026
00:42:08,000 --> 00:42:10,000
ALSO FOUND THAT SHE WAS ALMOST

1027
00:42:10,000 --> 00:42:13,840
HIGH FOR THE RIGHT MUTATION

1028
00:42:13,840 --> 00:42:18,520
WHICH IS AND SO WE MUTATIONS AND

1029
00:42:18,520 --> 00:42:20,200
WE START WITH THIS AND WE LOOKED

1030
00:42:20,200 --> 00:42:23,120
ANOTHER THE LOCATIONS

1031
00:42:23,120 --> 00:42:26,920
LIMITATIONS AND AROUND THE AMINO

1032
00:42:26,920 --> 00:42:30,680
ACID 136 AND CRITICAL FOR TWO

1033
00:42:30,680 --> 00:42:33,880
FUNCTIONS, BINDS TO THE LDL

1034
00:42:33,880 --> 00:42:39,160
RECEPTOR AND THE GLYCO SAM INK

1035
00:42:39,160 --> 00:42:40,920
OWE GLYCANS SO PREVIOUS WORK BY

1036
00:42:40,920 --> 00:42:42,360
OTHERS AND HAS SHOWN AND YOU

1037
00:42:42,360 --> 00:42:43,560
PROBABLY HAVE FAMILIAR WITH THIS

1038
00:42:43,560 --> 00:42:45,840
AS WELL THAT THE LDL RECEPTORS

1039
00:42:45,840 --> 00:42:48,560
HAS A HIGH AFFINITY WITH 8.4

1040
00:42:48,560 --> 00:42:53,600
FOLLOWED BY 8.3 AND FOLLOWED BY

1041
00:42:53,600 --> 00:42:55,680
SOMETHING RATE NOW AND IT HAS

1042
00:42:55,680 --> 00:42:58,640
AFFINITY ABOUT 30% AND BIND TO

1043
00:42:58,640 --> 00:43:00,400
GO THESE LDL BUT IT'S SOMETHING

1044
00:43:00,400 --> 00:43:02,760
THAT I WAS KNOWN BY THEN AND IT

1045
00:43:02,760 --> 00:43:04,480
WAS LIKE THE CHRISTCHURCH FOR

1046
00:43:04,480 --> 00:43:07,120
INSTANCE IN THIS BINDING WITH

1047
00:43:07,120 --> 00:43:08,320
HSPG AND THERE WAS SOMETHING

1048
00:43:08,320 --> 00:43:10,880
THAT BASED ON THE LOCATION, AS I

1049
00:43:10,880 --> 00:43:12,360
MENTIONED IT WAS LIKE PREDICTED

1050
00:43:12,360 --> 00:43:13,960
BUT IT WAS NOT AT THE TIME AND

1051
00:43:13,960 --> 00:43:17,280
AT LEAST IT WAS NOT REPORTED IN

1052
00:43:17,280 --> 00:43:18,280
THE LEADERSHIP AND IT WAS CLEAR

1053
00:43:18,280 --> 00:43:20,960
AND RELEVANT AT THAT POINT AND

1054
00:43:20,960 --> 00:43:23,560
GOING AFTER HSPG WAS IMPORTANT

1055
00:43:23,560 --> 00:43:27,720
BECAUSE YOU CAN SEE HERE, HSPG

1056
00:43:27,720 --> 00:43:29,720
IS IMPLICATED IN STEPS OF THE

1057
00:43:29,720 --> 00:43:31,280
PATHOLOGY OF ALZHEIMER'S DISEASE

1058
00:43:31,280 --> 00:43:33,240
INCLUDING THE REGULATION OF THIS

1059
00:43:33,240 --> 00:43:39,320
ACTIVITY AND REGULATION AMYLOID

1060
00:43:39,320 --> 00:43:42,800
AND INFLAMMATION AND TAU OUT

1061
00:43:42,800 --> 00:43:44,360
TAKE AND IT WAS INTERESTING FOR

1062
00:43:44,360 --> 00:43:49,160
US TO SEE THAT MAYBE FOR SOME

1063
00:43:49,160 --> 00:43:52,440
KIND OF IT WAS 30 YEARS FOR

1064
00:43:52,440 --> 00:43:54,480
SOMEONE IN THE KINDRED MAYBE FOR

1065
00:43:54,480 --> 00:43:56,600
SOMETHING LIKE THAT, THE

1066
00:43:56,600 --> 00:44:00,000
MECHANISMS AND THE PROTECTION

1067
00:44:00,000 --> 00:44:01,200
NODED TO BE SOMETHING THAT

1068
00:44:01,200 --> 00:44:03,520
CROSSED THE PATHOLOGY OR TIME OF

1069
00:44:03,520 --> 00:44:04,560
DISEASE AT DIFFERENT LEVELS ALL

1070
00:44:04,560 --> 00:44:09,880
THE WAY FROM AMYLOID TO PATH OLE

1071
00:44:09,880 --> 00:44:13,280
GOUGH AND IT MIGHT BE SOMETHING

1072
00:44:13,280 --> 00:44:15,160
LIKE BASE COULD PROVIDE THAT

1073
00:44:15,160 --> 00:44:17,120
ANSWER AND I PASS IT TO MY

1074
00:44:17,120 --> 00:44:18,960
COLLEAGUES, THE BASIC

1075
00:44:18,960 --> 00:44:20,720
SCIENTISTS, AND SOME OF THE

1076
00:44:20,720 --> 00:44:21,480
EXPERIMENTS THAT WERE CONDUCTED

1077
00:44:21,480 --> 00:44:25,360
HERE AND IT WAS ACTUALLY

1078
00:44:25,360 --> 00:44:29,400
CONDUCTED AT A LAB IN POSTDOCS

1079
00:44:29,400 --> 00:44:32,040
AND ONE OF THE FIRST EXMENTS TO

1080
00:44:32,040 --> 00:44:34,200
START UNDER THE MOLECULAR

1081
00:44:34,200 --> 00:44:36,000
CONSEQUENCES OF A CHRISTCHURCH

1082
00:44:36,000 --> 00:44:39,400
AND THE FIRST ONE THEY MEASURED

1083
00:44:39,400 --> 00:44:42,160
INVOTE ROW AND THEY ACTUALLY

1084
00:44:42,160 --> 00:44:43,320
FOUND THAT CHRISTCHURCH WAS A

1085
00:44:43,320 --> 00:44:48,160
COMPARED TO THE 8.3 AND HAD

1086
00:44:48,160 --> 00:44:50,760
LOWER AGGREGATION AND IN THE

1087
00:44:50,760 --> 00:44:54,720
SECOND SET OF THE EXPERIMENTS

1088
00:44:54,720 --> 00:44:56,120
THEY USED A JUST TO START

1089
00:44:56,120 --> 00:44:59,480
UNDERSTANDING THIS INTERACTIONS

1090
00:44:59,480 --> 00:45:01,240
BETWEEN CHRISTCHURCH AND HSPG

1091
00:45:01,240 --> 00:45:06,400
AND THEY FOUND THAT THE

1092
00:45:06,400 --> 00:45:08,160
INTERACTION OF THE 8.4 WAS

1093
00:45:08,160 --> 00:45:10,120
STRONG AND IT WAS LESS STRONG

1094
00:45:10,120 --> 00:45:16,920
WITH THE POINT HERE.

1095
00:45:16,920 --> 00:45:18,480
IT WAS STONG WITH 8.2 AND WHAT

1096
00:45:18,480 --> 00:45:20,960
WAS REMARKABLE WAS THE

1097
00:45:20,960 --> 00:45:23,360
ASSOCIATION WITH 8.3 CHRIST HER

1098
00:45:23,360 --> 00:45:24,920
WAS MUCH WEAKER COMPARED TO THE

1099
00:45:24,920 --> 00:45:26,320
OTHER AND IT'S SOMETHING YOU CAN

1100
00:45:26,320 --> 00:45:27,040
SEE HERE.

1101
00:45:27,040 --> 00:45:31,720
QUITE REMARKABLE, THE WEAKEST

1102
00:45:31,720 --> 00:45:34,040
STRAINS OF THE ASSOCIATION THAT

1103
00:45:34,040 --> 00:45:36,360
WAS OBSERVED WAS IN ONE WITH A

1104
00:45:36,360 --> 00:45:36,920
CHRISTCHURCH.

1105
00:45:36,920 --> 00:45:39,920
AND THEN, AS A PROOF OF

1106
00:45:39,920 --> 00:45:43,440
PRINCIPLE WE DESIGNED AND TEST

1107
00:45:43,440 --> 00:45:44,920
WHETHER THESE MECHANISMS COULD

1108
00:45:44,920 --> 00:45:47,240
BE TRANSLATED IN THE FUTURE AND

1109
00:45:47,240 --> 00:45:50,480
IT WOULD DESIGN AN ANTI BODY TO

1110
00:45:50,480 --> 00:45:52,680
MIMIC THE ROLE OF THE

1111
00:45:52,680 --> 00:45:53,440
CHRISTCHURCH AROUND THIS

1112
00:45:53,440 --> 00:45:56,040
LOCATION AND AS WE 136 AND THIS

1113
00:45:56,040 --> 00:45:58,520
IS PRESENTED HERE.

1114
00:45:58,520 --> 00:46:02,440
PRETTY MUCH YOU CAN SEE, YOU CAN

1115
00:46:02,440 --> 00:46:05,080
ACTUALLY SEE WHEN YOU USE THE

1116
00:46:05,080 --> 00:46:09,480
ANTIBODY THAT RECOGNIZED THE

1117
00:46:09,480 --> 00:46:17,160
APOE THE ANTIBODY THAT RECOGNIZE

1118
00:46:17,160 --> 00:46:20,400
APOE3 MIMICS THE INHIBITING THE

1119
00:46:20,400 --> 00:46:22,440
BINDING TO PRETTY MUCH ALL

1120
00:46:22,440 --> 00:46:25,400
TOGETHER, THE CONCLUSION OF

1121
00:46:25,400 --> 00:46:30,120
THESE THREE EXPERIMENTS,

1122
00:46:30,120 --> 00:46:31,160
CHRISTCHURCH IN VITRO REGULATES

1123
00:46:31,160 --> 00:46:33,680
AND MODULATES DEROGATION OR

1124
00:46:33,680 --> 00:46:38,160
AMYLOID WHICH IS INTRIGUING

1125
00:46:38,160 --> 00:46:39,880
ITSELF AND THEY HAVE A LOT OF

1126
00:46:39,880 --> 00:46:41,680
AMYLOID ON HER BRAIN SO IT COULD

1127
00:46:41,680 --> 00:46:46,120
HAVE BEEN WORSE IS THERE WAS NO

1128
00:46:46,120 --> 00:46:49,480
CHRISTCHURCH THERE AND WE FOUND

1129
00:46:49,480 --> 00:46:52,160
THEY IMPAIR THIS BINDING AND

1130
00:46:52,160 --> 00:46:55,400
ALSO WE SHOW AN ANTI BODY THAT

1131
00:46:55,400 --> 00:46:57,160
RECOGNIZES APOE3 AROUND THIS

1132
00:46:57,160 --> 00:47:00,800
REGION OF AMINO ACID 136 WHERE

1133
00:47:00,800 --> 00:47:07,280
CHRIST CHRISTCHURCH COULD SUGGEA

1134
00:47:07,280 --> 00:47:09,920
POTENTIAL THERAPEUTIC AND BASED

1135
00:47:09,920 --> 00:47:13,240
ON THESE FINDINGS, MY

1136
00:47:13,240 --> 00:47:16,560
COLLABORATORS AND MY OTHERS ARE

1137
00:47:16,560 --> 00:47:18,200
PURSUING POTENTIAL THERAPEUTIC

1138
00:47:18,200 --> 00:47:19,960
SO THE MAIN CONCLUSION OF THIS

1139
00:47:19,960 --> 00:47:23,760
CASE IS LIKE THE SAME THAT THE

1140
00:47:23,760 --> 00:47:27,040
IMPACT OR APOE IS NOT LIMITED TO

1141
00:47:27,040 --> 00:47:28,880
AMYLOID AGGREGATION AND IT'S

1142
00:47:28,880 --> 00:47:30,480
ALSO SOMETHING THAT MAY IMPACT

1143
00:47:30,480 --> 00:47:35,320
OUR DIRECTLY OR INDIRECTLY THE

1144
00:47:35,320 --> 00:47:36,240
EFFECT TAU PROPAGATION AND WE

1145
00:47:36,240 --> 00:47:39,520
LEARNED THAT THIS PROTECTION

1146
00:47:39,520 --> 00:47:40,320
ESPECIALLY IN LID WHY'S CASE MAY

1147
00:47:40,320 --> 00:47:42,480
BE AT LEAST IN PART BY THE

1148
00:47:42,480 --> 00:47:43,960
MAGNITUDE OF THESE BINDINGS

1149
00:47:43,960 --> 00:47:48,600
BETWEEN APOE-HSPG AND WE LEARNED

1150
00:47:48,600 --> 00:47:50,280
THAT MAYBE ANTIBODIES, SOMETHING

1151
00:47:50,280 --> 00:47:56,880
THAT IS A SMALL MOLECULE MAY

1152
00:47:56,880 --> 00:47:59,640
INTERFERE BETWEEN APOE AND HSPG

1153
00:47:59,640 --> 00:48:02,240
CAN REDUCE THE FUNCTIONS MAY

1154
00:48:02,240 --> 00:48:07,520
ACTUALLY HAVE A MAJOR IMPACT SO

1155
00:48:07,520 --> 00:48:09,080
WE HAVE BEEN WORKING ON THESE

1156
00:48:09,080 --> 00:48:11,320
FOR THE PAST FEW YEARS AND

1157
00:48:11,320 --> 00:48:13,640
HOPEFULLY THE FUTURE I CAN SHARE

1158
00:48:13,640 --> 00:48:17,200
MORE ABOUT THESE UPDATES BUT

1159
00:48:17,200 --> 00:48:18,600
LIKE WORKING OF COURSE IN

1160
00:48:18,600 --> 00:48:19,960
UNDERSTANDING THE MECHANISMS ON

1161
00:48:19,960 --> 00:48:21,440
THESE NEURO PROTECTION AND

1162
00:48:21,440 --> 00:48:24,880
RUNNING MODERN INVETO AND

1163
00:48:24,880 --> 00:48:27,400
MODELS, WE ARE ALSO WORK AND I'M

1164
00:48:27,400 --> 00:48:29,120
GOING TO BRIEFLY MENTION THE

1165
00:48:29,120 --> 00:48:30,360
WORK WORE DOING UNDERSTANDING

1166
00:48:30,360 --> 00:48:34,640
THE IMPACT OR CHRISTCHURCH IN

1167
00:48:34,640 --> 00:48:36,280
PSYGOATS WHEN WE ONLY HAVE ONE

1168
00:48:36,280 --> 00:48:38,960
COPY AND AS I MENTIONED BEFORE,

1169
00:48:38,960 --> 00:48:40,600
SO, DONNA LYDIA IS ONLY THE

1170
00:48:40,600 --> 00:48:44,080
FIRST ONE IN THE PROTECT WE WERE

1171
00:48:44,080 --> 00:48:47,520
ABLE TO IDENTIFY OTHER OUTLIERS

1172
00:48:47,520 --> 00:48:49,760
AND WE ARE IN THE PROCESS OF

1173
00:48:49,760 --> 00:48:51,040
CHARACTERIZING THE OTHER ONES AS

1174
00:48:51,040 --> 00:48:51,560
WELL.

1175
00:48:51,560 --> 00:48:58,520
SO AS A QUICK UPDATE, SO, WITH

1176
00:48:58,520 --> 00:49:03,200
Dr. LOPITA IF APOE

1177
00:49:03,200 --> 00:49:06,160
CHRISTCHURCH CAN BE PROTECTIVE

1178
00:49:06,160 --> 00:49:08,680
IN COLLABORATION WITH DOCTORS,

1179
00:49:08,680 --> 00:49:14,080
WE ACTUALLY CHARACTERIZE APOE IN

1180
00:49:14,080 --> 00:49:16,200
2,000 FROM THE CARRIERS FROM THE

1181
00:49:16,200 --> 00:49:18,960
COLUMBIAN CARRIERS INCLUDING THE

1182
00:49:18,960 --> 00:49:20,960
CHRISTCHURCH MUTATION AND WE

1183
00:49:20,960 --> 00:49:24,560
ACTUALLY IDENTIFIED 97 OF THE

1184
00:49:24,560 --> 00:49:26,920
MEMBERS THAT HAVE THE

1185
00:49:26,920 --> 00:49:29,680
CHRISTCHURCH MUTATION INCLUDING

1186
00:49:29,680 --> 00:49:33,120
84 WHO ARE LIVING AND 13 WHO ARE

1187
00:49:33,120 --> 00:49:35,880
DECEASED BUT OUT OF THOSE 13

1188
00:49:35,880 --> 00:49:37,200
SEVEN WERE BRYN DONORS AND OUT

1189
00:49:37,200 --> 00:49:41,720
OF THESE 84, 29 OF THEM ACTUAL

1190
00:49:41,720 --> 00:49:47,280
LOW HAVE BOTH MUTATIONS AND THE

1191
00:49:47,280 --> 00:49:51,720
APOE3 AND THE E280A VARIATION SO

1192
00:49:51,720 --> 00:49:53,520
WE'RE FALLING THIS 84 AND

1193
00:49:53,520 --> 00:49:58,000
CHARACTER EYES THIS IN THE PAST

1194
00:49:58,000 --> 00:50:00,480
YEAR SO IN THE PAST YEAR, ALL

1195
00:50:00,480 --> 00:50:03,480
THE 84 WERE RECONTACTED AND THEY

1196
00:50:03,480 --> 00:50:05,120
STARTED UNDERGOING COMPREHENSIVE

1197
00:50:05,120 --> 00:50:09,400
CLINICAL ASSESSMENTS, MIs AND

1198
00:50:09,400 --> 00:50:11,280
PRETTY MUCH ALL THE IMAGING THAT

1199
00:50:11,280 --> 00:50:17,280
CAN BE DONE IN COLOMBIA AND

1200
00:50:17,280 --> 00:50:18,080
SO -- SORRY.

1201
00:50:18,080 --> 00:50:21,240
DID I DO SOMETHING WRONG?

1202
00:50:21,240 --> 00:50:23,840
THE AGE RANGE FOR THE CARRIERS

1203
00:50:23,840 --> 00:50:29,560
GOES FROM 17 TO 72 YEARS AND

1204
00:50:29,560 --> 00:50:31,560
ENCLOUDS 11 THAT HAVE THE TWO

1205
00:50:31,560 --> 00:50:34,680
MUTATIONS THAT ACTUALLY ARE FROM

1206
00:50:34,680 --> 00:50:37,160
50 TO 72 AND FROM THOSE I PRETTY

1207
00:50:37,160 --> 00:50:46,400
MUCH AS I MENTIO MENTION BEF 50Y

1208
00:50:46,400 --> 00:50:49,160
OLDER AND WE ONLY CHARACTERIZE

1209
00:50:49,160 --> 00:50:53,160
FOR AIC SO WE'RE SAYING THIS SO

1210
00:50:53,160 --> 00:50:54,720
FOR CHARACTERIZING THE FIRST

1211
00:50:54,720 --> 00:50:57,120
THROW, THE COGNITIVE PERFORMANCE

1212
00:50:57,120 --> 00:51:00,080
THAT WE REVIEW FOR THIS

1213
00:51:00,080 --> 00:51:02,360
INDIVIDUALS THEY ACTUALLY FELL

1214
00:51:02,360 --> 00:51:05,040
WITHIN THE NORMAL RANGE COMPARED

1215
00:51:05,040 --> 00:51:07,400
TO THE AGE MASS IN INDIVIDUALS

1216
00:51:07,400 --> 00:51:13,120
FROM TH THE KINDRED AND THE MRID

1217
00:51:13,120 --> 00:51:15,840
HOPEFULLY BY THE TIME THAT WE

1218
00:51:15,840 --> 00:51:17,600
PRESENTED IT, WE WILL HAVE DATA

1219
00:51:17,600 --> 00:51:19,400
ON THOSE INDIVIDUALS AS WELL.

1220
00:51:19,400 --> 00:51:20,920
SO WE HAVE ONE INDIVIDUAL THAT

1221
00:51:20,920 --> 00:51:24,480
ACTUAL LOW HAD A TRAVEL TO

1222
00:51:24,480 --> 00:51:26,400
BOSTON FOR TAU IMAGES AND GOING

1223
00:51:26,400 --> 00:51:30,520
BACK TO THE CORTEX THIS IS HOW

1224
00:51:30,520 --> 00:51:32,200
THEY TAU IMAGING LOCKS FOR

1225
00:51:32,200 --> 00:51:34,360
SOMEONE WITH ONLY ONE COPY AND

1226
00:51:34,360 --> 00:51:37,720
SO THE SAYING LIKE IT COMPARED

1227
00:51:37,720 --> 00:51:40,040
TO ANYBODY IN THE KINDRED, EVEN

1228
00:51:40,040 --> 00:51:49,240
AFTER TWO YEARS OF FOLLOW-UP SO

1229
00:51:49,240 --> 00:51:52,560
THIS IS PRELIMINARY BUT FIRST

1230
00:51:52,560 --> 00:51:56,040
THE PREVALENCE RATE OF

1231
00:51:56,040 --> 00:51:57,800
CHRISTCHURCH AND IT'S VERY HIGH

1232
00:51:57,800 --> 00:51:59,960
COMPARED TO THE GENERAL

1233
00:51:59,960 --> 00:52:01,440
POPULATION AND IT'S SOMETHING

1234
00:52:01,440 --> 00:52:04,520
THAT THE FIRST BIG NEWS THERE

1235
00:52:04,520 --> 00:52:07,040
AND THE PRELIMINARY DATA THAT WE

1236
00:52:07,040 --> 00:52:09,840
HAVE IS VERY PRELIMINARY BUT

1237
00:52:09,840 --> 00:52:11,920
TALKS THEY MAY HAVE SOME LEVEL

1238
00:52:11,920 --> 00:52:17,560
OF PROTECTION WITHIN THE TWO

1239
00:52:17,560 --> 00:52:22,000
STUDY AND WE NEED TO CONTINUE

1240
00:52:22,000 --> 00:52:23,360
WITH THE CHARACTERIZATION BUT

1241
00:52:23,360 --> 00:52:28,240
THE IDEA IS TO SEE IF

1242
00:52:28,240 --> 00:52:29,440
CHRISTCHURCH CAN ONLY PROTECTED

1243
00:52:29,440 --> 00:52:31,880
FOR THE ONES IN BRAZIL AND ONE

1244
00:52:31,880 --> 00:52:33,480
MUTATION SO AWFUL THESE ARE THE

1245
00:52:33,480 --> 00:52:35,080
SAME TO HOW MUCH WE CAN ACTUALLY

1246
00:52:35,080 --> 00:52:36,560
LEARN FROM ONE PATIENT AND THIS

1247
00:52:36,560 --> 00:52:38,560
IS GOING BACK TO THE CLINIC,

1248
00:52:38,560 --> 00:52:40,720
IT'S IMPORTANT TO TAKE IT FROM

1249
00:52:40,720 --> 00:52:42,040
THE CLINIC AND HOW MUCH ONE

1250
00:52:42,040 --> 00:52:44,760
PATIENT CAN TEACH US ABOUT

1251
00:52:44,760 --> 00:52:46,280
GENOMICS AND BASIC SIGNS AND

1252
00:52:46,280 --> 00:52:48,120
HOPEFULLY IN THE FUTURE OR SO

1253
00:52:48,120 --> 00:52:49,840
THEY TEACH US DRUG DISCOVERY AND

1254
00:52:49,840 --> 00:52:53,000
CLINICAL TRIALS AND TO CONCLUDE,

1255
00:52:53,000 --> 00:52:55,240
SO HOPEFULLY I CONVINCE YOU THAT

1256
00:52:55,240 --> 00:52:58,360
THEY WORK WITH THE FAMILIES AND

1257
00:52:58,360 --> 00:53:02,760
MUTATIONS AND PROVIDE A UNIQUE

1258
00:53:02,760 --> 00:53:05,760
OPPORTUNITY TO CLINICAL TO

1259
00:53:05,760 --> 00:53:08,880
CLINICAL STAGES AND TO DEVELOP

1260
00:53:08,880 --> 00:53:09,720
INFORMATIONS FOR EARLY DOUGH

1261
00:53:09,720 --> 00:53:12,440
TEXT TO AVAILABLE INTERVENTIONS

1262
00:53:12,440 --> 00:53:17,560
AND CLINICAL TRIALS AND DEVELOP

1263
00:53:17,560 --> 00:53:20,480
FOR CHARACTERIZE THE BIOMARKER

1264
00:53:20,480 --> 00:53:21,760
TRAJECTORY AND THERE'S MORE TO

1265
00:53:21,760 --> 00:53:24,200
LEARN FROM THIS AND MUTATIONS

1266
00:53:24,200 --> 00:53:27,080
AND THOSE INDIVIDUALS THAT ARE

1267
00:53:27,080 --> 00:53:28,400
UNIMPAIRED AND SO WE SHOULD

1268
00:53:28,400 --> 00:53:33,600
ENCLOUD MORE FAMILIAR LESS IN LE

1269
00:53:33,600 --> 00:53:33,960
FUTURE.

1270
00:53:33,960 --> 00:53:35,440
THIS TAKES A VILLAGE AND I WOULD

1271
00:53:35,440 --> 00:53:37,560
LIKE TO ACKNOWLEDGE EVERYBODY

1272
00:53:37,560 --> 00:53:38,760
THAT'S BEEN PART OF THE CALL OF

1273
00:53:38,760 --> 00:53:40,840
THIS STUDY.

1274
00:53:40,840 --> 00:53:45,080
EVERYBODY IN MY LAB, MY MENTORS,

1275
00:53:45,080 --> 00:53:48,880
AND THE DOCTORS AND

1276
00:53:52,560 --> 00:53:54,160
THE FAMILIES IN COLOMBIA FOR

1277
00:53:54,160 --> 00:53:56,640
THEIR DEDICATION TO RESEARCH AND

1278
00:53:56,640 --> 00:53:58,280
MY FUNDING IN SUPPORT AS WELL.

1279
00:53:58,280 --> 00:53:59,320
THANK YOU, VERY MUCH.

1280
00:53:59,320 --> 00:54:05,560
 [APPLAUSE]

1281
00:54:05,560 --> 00:54:07,000
>> WOULD YOU LIKE TO START
WITH

1282
00:54:07,000 --> 00:54:07,280
A QUESTION?

1283
00:54:07,280 --> 00:54:09,080
I HAVE A FEW MORE.

1284
00:54:09,080 --> 00:54:13,080
FIRST, LET ME REPEAT THAT THE

1285
00:54:13,080 --> 00:54:18,960
CNE CODE AND THAT IS 37950.

1286
00:54:18,960 --> 00:54:23,120
I'LL ASK ONE QUESTION.

1287
00:54:23,120 --> 00:54:27,920
I'LL TRY TO READ THIS LOWLY.

1288
00:54:27,920 --> 00:54:31,240
HEPERIN SULPHATE PROTO GAELYNN

1289
00:54:31,240 --> 00:54:33,040
ARE FOR MODE ABLE HUMAN VIRUSES.

1290
00:54:33,040 --> 00:54:36,240
WHEN YOU LOOKED FOR SIGNS OF

1291
00:54:36,240 --> 00:54:39,840
VIRUS INFECTION AS A POSSIBLE

1292
00:54:39,840 --> 00:54:41,240
RISK OR PROTECTION FACTOR?

1293
00:54:41,240 --> 00:54:42,880
>> THAT'S A GOOD POINT.

1294
00:54:42,880 --> 00:54:44,480
NO WE HAVEN'T BUT WE SHOULD,

1295
00:54:44,480 --> 00:54:44,680
YEAH.

1296
00:54:44,680 --> 00:54:46,680
>> THANK YOU.

1297
00:54:46,680 --> 00:54:47,600
>> YEAH.

1298
00:54:47,600 --> 00:54:49,720
>> COUPLE OF QUESTIONS.

1299
00:54:49,720 --> 00:54:51,480
FIRST, AMONG THE MANY STRIKING

1300
00:54:51,480 --> 00:54:53,640
FINDINGS, ONE WAS MENTIONED IF I

1301
00:54:53,640 --> 00:54:55,120
HEARD CORRECTLY IS THAT CARRIERS

1302
00:54:55,120 --> 00:54:57,760
HAD AN INCREASE IN SINGULAR

1303
00:54:57,760 --> 00:54:58,800
CORTEX GRAY MATTER.

1304
00:54:58,800 --> 00:55:00,360
DO YOU HAVE ANY IDEA WHAT MAKES

1305
00:55:00,360 --> 00:55:07,480
UP THAT INCREASED MASS?

1306
00:55:07,480 --> 00:55:07,800
NO.

1307
00:55:07,800 --> 00:55:08,840
ONE OF THE ISSUES WE DISCUSSED

1308
00:55:08,840 --> 00:55:10,440
IN THE PAPER AND THIS IS LIKE

1309
00:55:10,440 --> 00:55:13,640
GOING BACK TO THE COMMUNITY

1310
00:55:13,640 --> 00:55:14,720
REFERS TO THE FINDINGS IN THE

1311
00:55:14,720 --> 00:55:17,960
LIFESPAN AND THE CHILDREN.

1312
00:55:17,960 --> 00:55:19,280
ONE OF THE THINGS WE DISCUSSED

1313
00:55:19,280 --> 00:55:26,560
IT COULD BE RELATED WITH

1314
00:55:26,560 --> 00:55:26,920
INFLAMMATION.

1315
00:55:26,920 --> 00:55:29,920
>> IT'S EARLY SO YOU DON'T
HAVE

1316
00:55:29,920 --> 00:55:30,840
POSTMORTEM EXAMINATION YET.

1317
00:55:30,840 --> 00:55:31,360
>> EXACTLY.

1318
00:55:31,360 --> 00:55:33,320
>> ANOTHER VERY DIFFERENT

1319
00:55:33,320 --> 00:55:38,760
QUESTION, IN THE I DO DIANNE

1320
00:55:38,760 --> 00:55:40,880
STUDY, THEY LOOKED AT MUCH

1321
00:55:40,880 --> 00:55:42,440
SMALLER INDIVIDUAL FAMILIES AND

1322
00:55:42,440 --> 00:55:43,840
MULTIPLE OTHER OF THEM A CROSS

1323
00:55:43,840 --> 00:55:44,440
THE WORLD.

1324
00:55:44,440 --> 00:55:46,600
I JUST KNOW THE BEHAVIOR OF THE

1325
00:55:46,600 --> 00:55:48,000
SOCIOLOGY OF THAT FAMILY OFTEN

1326
00:55:48,000 --> 00:55:50,160
THEY DO WANT TO KNOW THEIR

1327
00:55:50,160 --> 00:55:52,240
TYPING AND IT LEADS TO

1328
00:55:52,240 --> 00:55:53,200
INTERESTING STRATEGIES FOR

1329
00:55:53,200 --> 00:55:54,640
CLINICAL STUDIES AND TRIALS.

1330
00:55:54,640 --> 00:55:59,800
CAN YOU COMMENT ON WAS THERE A

1331
00:55:59,800 --> 00:56:00,720
PHENOMENON IN THE COLOMBIA

1332
00:56:00,720 --> 00:56:01,080
COHORT?

1333
00:56:01,080 --> 00:56:03,560
>> THEY DON'T WANT TO KNOW
THE

1334
00:56:03,560 --> 00:56:04,120
STATUS.

1335
00:56:04,120 --> 00:56:07,080
>> THIS IS VERY GOOD
QUESTION.

1336
00:56:07,080 --> 00:56:09,080
RIGHT NOW FOR INSTANCE, WE ARE

1337
00:56:09,080 --> 00:56:11,440
GOING TO PRESENT SOME OF THE

1338
00:56:11,440 --> 00:56:14,880
RESORTS OF THE PILOT STUDY

1339
00:56:14,880 --> 00:56:18,080
CONDUCTED ABOUT THAT SO WE

1340
00:56:18,080 --> 00:56:19,600
PRETTY MUCH I DON'T WANT TO TELL

1341
00:56:19,600 --> 00:56:23,120
YOU EVERYTHING THAT'S GOING TO

1342
00:56:23,120 --> 00:56:25,600
BE THERE BUT NUCLEAR FAMILY BY

1343
00:56:25,600 --> 00:56:27,600
NUCLEAR FAMILY SO THERE ARE SOME

1344
00:56:27,600 --> 00:56:28,880
FAMILIES THAT THEY ARE MORE

1345
00:56:28,880 --> 00:56:30,720
INCLINED TO KNOW AND SOME OTHER

1346
00:56:30,720 --> 00:56:32,720
FAMILIES THEY REALLY DON'T WANT

1347
00:56:32,720 --> 00:56:33,640
TO KNOW.

1348
00:56:33,640 --> 00:56:37,280
SO YEAH.

1349
00:56:37,280 --> 00:56:39,160
IT VARIES.

1350
00:56:39,160 --> 00:56:42,680
>> THIS IS FROM ONE OF OUR

1351
00:56:42,680 --> 00:56:43,200
RESEARCHERS HERE.

1352
00:56:43,200 --> 00:56:50,200
VERY BEAUTIFUL RESULTS.

1353
00:56:50,200 --> 00:56:51,520
EXALT OF THE DATA AND TESTING

1354
00:56:51,520 --> 00:56:55,600
PRESENTED RELATED DIRECTLY TO

1355
00:56:55,600 --> 00:56:56,280
AMYLOID AND TAU.

1356
00:56:56,280 --> 00:56:58,120
WHAT IS THE DATA AVAILABLE

1357
00:56:58,120 --> 00:57:00,160
RELATED TO THE INFLAMMATORY

1358
00:57:00,160 --> 00:57:04,440
ASPECTS OF THE DISEASE IN THIS

1359
00:57:04,440 --> 00:57:04,920
KINDRED.

1360
00:57:04,920 --> 00:57:06,680
BLOOD OR PET BIOMARKERS THAT

1361
00:57:06,680 --> 00:57:07,400
WERE DONE?

1362
00:57:07,400 --> 00:57:08,920
THIS MAY BE ESPECIALLY IMPORTANT

1363
00:57:08,920 --> 00:57:11,720
IN THE APOE CARRIERS AS WELL.

1364
00:57:11,720 --> 00:57:13,760
>> THAT'S AN EXCELLENT
QUESTION.

1365
00:57:13,760 --> 00:57:16,480
THE ANSWER IS LIKE WE ACTUALLY

1366
00:57:16,480 --> 00:57:18,160
HAVE MARKERS OF THE NEW

1367
00:57:18,160 --> 00:57:19,560
INFLAMMATION YET BUT AS I

1368
00:57:19,560 --> 00:57:21,640
MENTIONED IN ONE OF THE SLIDES,

1369
00:57:21,640 --> 00:57:24,200
IT'S SOMETHING THAT IS ON GOING

1370
00:57:24,200 --> 00:57:27,280
SO NOW WE'RE COLLECTING

1371
00:57:27,280 --> 00:57:28,840
ESPECIALLY CSF AND WE ARE GOING

1372
00:57:28,840 --> 00:57:31,040
TO START MEASURING MARKERS ON

1373
00:57:31,040 --> 00:57:33,440
INFLAMMATION IN CSF IN THE

1374
00:57:33,440 --> 00:57:35,560
FUTURE WE ARE HARD TO MEASURE IN

1375
00:57:35,560 --> 00:57:37,440
PLASMA BUT MARKERS ON THE

1376
00:57:37,440 --> 00:57:39,480
INFLAMMATION IS TO MEASURE IN

1377
00:57:39,480 --> 00:57:41,720
CSF SO WE'RE COLLECTING IT AND

1378
00:57:41,720 --> 00:57:44,120
WE'LL HAVE AN ANSWER FOR THAT

1379
00:57:44,120 --> 00:57:47,280
BUT WE HAVEN'T DONE IT YET.

1380
00:57:47,280 --> 00:57:49,480
>>THANK YOU VERY MUCH,
THAT WAS

1381
00:57:49,480 --> 00:57:52,120
BEAUTIFUL PRESENTATION.

1382
00:57:52,120 --> 00:57:57,240
IN REGARD TO THE PET IMAGES ON

1383
00:57:57,240 --> 00:57:59,160
THE COLOMBIA KINDRED, CAN YOU

1384
00:57:59,160 --> 00:58:03,520
TELL IF THEY HAD A SIMILAR

1385
00:58:03,520 --> 00:58:05,880
HETERO AGAIN EIGHT TEE WHAT IS

1386
00:58:05,880 --> 00:58:07,600
DESCRIBED IN SPORADIC SOME THAT

1387
00:58:07,600 --> 00:58:10,120
ARE MORE LIKE POSTER YEAR AND

1388
00:58:10,120 --> 00:58:14,600
OTHER ANTERIOR AND OTHER HIM PA

1389
00:58:14,600 --> 00:58:17,360
CAM PA SPARING OR DO THEY LOCK

1390
00:58:17,360 --> 00:58:19,040
AT TAU IMAGING VERY SIMILAR,

1391
00:58:19,040 --> 00:58:20,360
PRETTY HOMOGENEOUS?

1392
00:58:20,360 --> 00:58:24,480
>> SO, I CAN GIVE YOU LIKE
TWO

1393
00:58:24,480 --> 00:58:24,960
ANSWERS.

1394
00:58:24,960 --> 00:58:28,280
SO THE FIRST ONE IS LIKE, SO,

1395
00:58:28,280 --> 00:58:30,920
THE SAMPLE THAT WE HAVE IS VERY

1396
00:58:30,920 --> 00:58:33,720
SMALL AND IT'S VERY HOMOGENEOUS

1397
00:58:33,720 --> 00:58:34,640
SO PRETTY MUCH LIKE FOR

1398
00:58:34,640 --> 00:58:36,760
INSTANCE, SOMETHING THAT WE HAVE

1399
00:58:36,760 --> 00:58:38,480
SEEN IS WE STARTED LIKE FOR

1400
00:58:38,480 --> 00:58:40,480
INSTANCE MEASURING TAU IN OTHER

1401
00:58:40,480 --> 00:58:41,880
MUTATIONS AND THE SAME WAY WE

1402
00:58:41,880 --> 00:58:44,000
STARTED LOOKING AT OTHER

1403
00:58:44,000 --> 00:58:51,760
MUTATIONS AND THE PARTING OF TAU

1404
00:58:51,760 --> 00:58:52,960
ACCUMULATION AND IT'S TENDS TO

1405
00:58:52,960 --> 00:58:56,520
BE A VERY HOME YO GENIOUS SO

1406
00:58:56,520 --> 00:58:58,000
WHEN YOU LOOK AT THE PAIRING

1407
00:58:58,000 --> 00:59:01,560
THAT WE HAVE IT'S VERY -- THE

1408
00:59:01,560 --> 00:59:03,240
PAIRING AND ACCUMULATION OR TAU

1409
00:59:03,240 --> 00:59:06,760
IS VERY TYPICAL OR WHAT IS

1410
00:59:06,760 --> 00:59:09,360
CALLED LIKE A YOU SEE IT AS

1411
00:59:09,360 --> 00:59:11,600
ALZHEIMER'S DISEASE AND AS SOON

1412
00:59:11,600 --> 00:59:13,960
AS YOU STUDY TO USE OTHER

1413
00:59:13,960 --> 00:59:20,720
MUTATIONS YOU START SEEING THE

1414
00:59:20,720 --> 00:59:21,080
HETERO GAIN TEE.

1415
00:59:21,080 --> 00:59:22,040
>> THIS ONE IS INTERESTING
SO I

1416
00:59:22,040 --> 00:59:23,600
WAS WONDERING THE SAME.

1417
00:59:23,600 --> 00:59:25,160
I SEEN STUDIES BACK AND FOURTH

1418
00:59:25,160 --> 00:59:27,360
SAYING COFFEE CONSUMPTION RAISES

1419
00:59:27,360 --> 00:59:28,800
THE RISK OF ALZHEIMER'S OR

1420
00:59:28,800 --> 00:59:29,480
REDUCES THE RISK.

1421
00:59:29,480 --> 00:59:31,200
THIS IS GREAT.

1422
00:59:31,200 --> 00:59:33,240
THIS DATA FROM COLOMBIA HAVE YOU

1423
00:59:33,240 --> 00:59:36,480
EXAMINED COFFEE CONSUMPTION IN

1424
00:59:36,480 --> 00:59:37,160
ALZHEIMER'S?

1425
00:59:37,160 --> 00:59:39,440
>> SO WE HAVEN'T.

1426
00:59:39,440 --> 00:59:42,720
SO YEAH, WE HAVEN'T AND WE

1427
00:59:42,720 --> 00:59:45,520
HAVEN'T ACTUALLY -- WELL, LET ME

1428
00:59:45,520 --> 00:59:45,720
SEE.

1429
00:59:45,720 --> 00:59:47,120
>> I DON'T KNOW IF THAT'S
AN

1430
00:59:47,120 --> 00:59:49,240
ASSUMPTION THAT COFFEE

1431
00:59:49,240 --> 00:59:50,480
CONSUMPTION IS HIGHER IN

1432
00:59:50,480 --> 00:59:51,520
COLOMBIA.

1433
00:59:51,520 --> 00:59:52,320
IT'S WHERE IT COMES FROM?

1434
00:59:52,320 --> 00:59:54,160
>> EVERYBODY DRINKS COFFEE
SO AT

1435
00:59:54,160 --> 00:59:57,560
END OF THE DAY WE WOULD HAVE IT.

1436
00:59:57,560 --> 01:00:00,360
SO WE ACTUAL WILL HE MENTIONED

1437
01:00:00,360 --> 01:00:01,800
LIKE, EATING HABITS, FOR

1438
01:00:01,800 --> 01:00:02,960
INSTANCE OR WE PROBABLY CAN'T

1439
01:00:02,960 --> 01:00:05,080
TAKE A LOOK AND SEE IF THERE'S

1440
01:00:05,080 --> 01:00:06,680
ANY DIFFERENT PARTICULAR LOW IS

1441
01:00:06,680 --> 01:00:09,840
HOW MANY THEY DRINK COFFEE AND

1442
01:00:09,840 --> 01:00:12,640
STUFF LIKE THAT SO WE'RE ALSO

1443
01:00:12,640 --> 01:00:13,640
MEASURING LIKE LIFESTYLE AND

1444
01:00:13,640 --> 01:00:15,320
STUFF LIKE THAT AND WE HAVE A

1445
01:00:15,320 --> 01:00:19,160
QUESTIONNAIRE ASKING FOR EATING

1446
01:00:19,160 --> 01:00:20,640
HABITS SO WE ASK WHAT THEY HAVE

1447
01:00:20,640 --> 01:00:22,040
AND WHAT THEY DRINK.

1448
01:00:22,040 --> 01:00:23,560
WE COULD LOOK AT THAT,

1449
01:00:23,560 --> 01:00:25,920
SPECIFICALLY BUT YEAH, WE

1450
01:00:25,920 --> 01:00:29,000
HAVEN'T ANALYZED THAT DATA YET.

1451
01:00:29,000 --> 01:00:30,560
EVERYBODY ACTUAL LOW HAS A

1452
01:00:30,560 --> 01:00:33,360
COFFEE IN THE MORNING SO IT'S

1453
01:00:33,360 --> 01:00:34,400
KIND OF LIKE, EVEN CARRIERS AND

1454
01:00:34,400 --> 01:00:35,360
NON CARRIERS.

1455
01:00:35,360 --> 01:00:38,800
WE CAN ACTUALLY LOOK AT THE

1456
01:00:38,800 --> 01:00:39,440
DATA.

1457
01:00:39,440 --> 01:00:42,440
>> ONE MORE QUICK ONE FROM
--

1458
01:00:42,440 --> 01:00:44,440
THANK YOU FOR THE FASCINATING

1459
01:00:44,440 --> 01:00:44,720
TALK.

1460
01:00:44,720 --> 01:00:46,040
PERHAPS I MISSED THIS, HOW LONG

1461
01:00:46,040 --> 01:00:48,480
HAS THE COLOMBIA CAN KINDRED

1462
01:00:48,480 --> 01:00:51,000
BEEN KNOWN AND THIS IS BASED IN

1463
01:00:51,000 --> 01:00:53,680
INDIGENOUS POPULATIONS OR

1464
01:00:53,680 --> 01:00:55,640
EUROPEAN/SPANISH POPULATIONS?

1465
01:00:55,640 --> 01:00:57,960
>> SO THE MUTATION IN
COLOMBIA

1466
01:00:57,960 --> 01:01:01,960
WAS DISCOVERED IN THE LATE

1467
01:01:01,960 --> 01:01:02,520
'80s.

1468
01:01:02,520 --> 01:01:04,200
SO THE ORIGINAL MUTATION WAS

1469
01:01:04,200 --> 01:01:09,720
ACTUALLY TRACKED BACK TO CON

1470
01:01:09,720 --> 01:01:10,400
KEYS DA DOR FROM SPAIN.

1471
01:01:10,400 --> 01:01:12,600
SO U.S. TRACKED TO SPAIN.

1472
01:01:12,600 --> 01:01:14,440
>> I WAS GOING TO ASK A
MORE

1473
01:01:14,440 --> 01:01:15,360
GENERAL FORM OF THE QUESTION

1474
01:01:15,360 --> 01:01:17,440
ABOUT COFFEE AND YOU ANSWERED IT

1475
01:01:17,440 --> 01:01:17,920
ALREADY.

1476
01:01:17,920 --> 01:01:19,680
IN ADDITION TO LOOKING AT

1477
01:01:19,680 --> 01:01:21,640
GENETIC RISK OF PROTECTIVE

1478
01:01:21,640 --> 01:01:22,800
FACTORS, IN THIS POPULATION WITH

1479
01:01:22,800 --> 01:01:25,600
A SING MANY HOMO GENIOUS

1480
01:01:25,600 --> 01:01:26,800
MUTATION, A PLACE TO LOOK FOR

1481
01:01:26,800 --> 01:01:29,600
OTHER NON GENETIC FACTORS AND

1482
01:01:29,600 --> 01:01:31,320
YOU ALREADY ANSWERED SO YOU LOCK

1483
01:01:31,320 --> 01:01:33,960
AT VARIOUS ENVIRONMENTAL

1484
01:01:33,960 --> 01:01:35,120
EXPOSURES THAT MIGHT BE

1485
01:01:35,120 --> 01:01:38,920
PROTECTIVE OR AGGRAVATED OR

1486
01:01:38,920 --> 01:01:39,760
ACCELERATED.

1487
01:01:39,760 --> 01:01:42,480
>> WE COLLECTED ALL THE
DATA,

1488
01:01:42,480 --> 01:01:42,840
YEAH.

1489
01:01:42,840 --> 01:01:45,080
THEY'RE LOOKING INTO THAT AND

1490
01:01:45,080 --> 01:01:48,560
SEE ABOUT THAT.

1491
01:01:48,560 --> 01:01:59,080
>> HAS THE COLOMBIA YAN
COHORT

1492
01:02:02,760 --> 01:02:03,080
STUDIES BRAINS.

1493
01:02:03,080 --> 01:02:03,920
>> YEAH.

1494
01:02:03,920 --> 01:02:06,040
>> ANY INTERESTING
REVELATION

1495
01:02:06,040 --> 01:02:06,440
THERE'S?

1496
01:02:06,440 --> 01:02:09,040
>> YOU MEAN FOR THE CASE
OF THE

1497
01:02:09,040 --> 01:02:10,640
CHRISTCHURCH?

1498
01:02:10,640 --> 01:02:11,000
>> YEAH.

1499
01:02:11,000 --> 01:02:11,960
THAT WOULD BE GREAT, YEAH.

1500
01:02:11,960 --> 01:02:13,480
>> FOR THE CASE OF THE

1501
01:02:13,480 --> 01:02:14,760
CHRISTCHURCH WE ARE CURRENTLY

1502
01:02:14,760 --> 01:02:16,400
WORKING ON THE POSTMORTEM AND I

1503
01:02:16,400 --> 01:02:17,440
DIDN'T MENTION IT BUT

1504
01:02:17,440 --> 01:02:19,200
UNFORTUNATELY THE PATIENT DIED

1505
01:02:19,200 --> 01:02:21,640
EARLY OVER A YEAR AGO AND THE

1506
01:02:21,640 --> 01:02:22,920
FAMILY ACTUALLY DONATED THE

1507
01:02:22,920 --> 01:02:25,320
BRAIN FOR ANALYSIS AND WE ARE

1508
01:02:25,320 --> 01:02:27,040
CURRENTLY WORKING ON THE AN AM

1509
01:02:27,040 --> 01:02:31,720
SIS AND THE SAME LIKE IN COLBOS

1510
01:02:31,720 --> 01:02:33,080
THEY'RE PRE CLINICAL AND THEY'RE

1511
01:02:33,080 --> 01:02:34,320
STILL VERY YOUNG BUT THE SAME IS

1512
01:02:34,320 --> 01:02:35,920
PART OF THE WORK WE DO WITH THE

1513
01:02:35,920 --> 01:02:37,800
FAMILIES WE ALWAYS TALK AND

1514
01:02:37,800 --> 01:02:39,200
BRING DONATION AND IN COLOMBIA

1515
01:02:39,200 --> 01:02:41,920
THEY ACTUALLY HAVE A NEURO BANK

1516
01:02:41,920 --> 01:02:45,880
AND BRAIN BANK THAT HAS OVER 300

1517
01:02:45,880 --> 01:02:47,240
BRAINS FROM THE MUTATIONS.

1518
01:02:47,240 --> 01:02:49,960
SO, YES, WE LIKE TO LOOK INTO

1519
01:02:49,960 --> 01:02:52,640
THAT AND EVERY TIME WE TALK

1520
01:02:52,640 --> 01:02:55,640
ABOUT THE IMPORTANCE OR DONATING

1521
01:02:55,640 --> 01:02:55,960
THE BRAINS.

1522
01:02:55,960 --> 01:02:57,240
>> TERRIFIC.

1523
01:02:57,240 --> 01:03:00,040
>> ONE OTHER QUESTION JUST
FOR

1524
01:03:00,040 --> 01:03:02,040
MY OWN KNOWLEDGE, YOU HAD TO

1525
01:03:02,040 --> 01:03:04,560
FIGURE WHERE YOU WERE LOCKING,

1526
01:03:04,560 --> 01:03:07,360
DIFFERENT PROFILES FOR AMYLOID

1527
01:03:07,360 --> 01:03:08,960
PATH OLE GOUGH AND THEN TAU

1528
01:03:08,960 --> 01:03:19,600
LEVELS OF TAU, AND YOU SAW THISP

1529
01:03:20,000 --> 01:03:21,680
SPIKE IN TAU AT 30 YEARS.

1530
01:03:21,680 --> 01:03:23,040
WHAT'S YOUR HYPOTHESIS OF WHAT

1531
01:03:23,040 --> 01:03:25,760
IS GOING ON IN THIS AGE-RELATED

1532
01:03:25,760 --> 01:03:27,360
MILESTONE THAT'S CAUSING THAT

1533
01:03:27,360 --> 01:03:30,680
SHARP INCREASE IN TAU?

1534
01:03:30,680 --> 01:03:32,960
>> SO, THE ANSWER IS I
DON'T

1535
01:03:32,960 --> 01:03:33,680
KNOW.

1536
01:03:33,680 --> 01:03:35,240
I THINK THAT DEFINITELY THERE'S

1537
01:03:35,240 --> 01:03:36,480
SOMETHING THERE THAT WE ARE

1538
01:03:36,480 --> 01:03:37,800
TRYING IDENTIFY WHAT IT IS AND

1539
01:03:37,800 --> 01:03:40,200
WHAT IS ON THE HYPOTHESIS LIKE

1540
01:03:40,200 --> 01:03:42,640
INFLAMMATION AND THAT IS THERE

1541
01:03:42,640 --> 01:03:43,720
IN BETWEEN AND SOMETHING ELSE

1542
01:03:43,720 --> 01:03:45,040
THAT I NEEDED TO MENTION BECAUSE

1543
01:03:45,040 --> 01:03:46,640
IT'S SOMETHING ELSE THAT WE'RE

1544
01:03:46,640 --> 01:03:48,920
EXPLORING IT COULD BE LIKE WHITE

1545
01:03:48,920 --> 01:03:50,560
MATTER FOR INSTANCE, THAT IS

1546
01:03:50,560 --> 01:03:52,920
SOMETHING THAT WE ARE CURRENTLY

1547
01:03:52,920 --> 01:03:54,160
EXAMINING AS WELL AND YEAH,

1548
01:03:54,160 --> 01:03:55,320
PROBABLY THERE'S ANOTHER FACT OR

1549
01:03:55,320 --> 01:03:58,520
THERE THAT IS ALSO CONTRIBUTING.

1550
01:03:58,520 --> 01:04:01,480
>> THANK YOU.

1551
01:04:01,480 --> 01:04:04,040
>> ANY CONCLUDING REMARKS?

1552
01:04:04,040 --> 01:04:06,120
>> I WANTED TO THANK YOU
SO MUCH

1553
01:04:06,120 --> 01:04:08,720
FOR FASCINATING TALK AND GREAT

1554
01:04:08,720 --> 01:04:14,480
ORIGINAL WORK AND MAYBE EXEMPLAR

1555
01:04:14,480 --> 01:04:16,920
THAT ONE CAN FIND A PLACE AND

1556
01:04:16,920 --> 01:04:19,800
NOVEL RESEARCH AREAS AND REAL

1557
01:04:19,800 --> 01:04:20,600
FIFTH EXCELERATE PROGRESS THE

1558
01:04:20,600 --> 01:04:22,560
WAY YOU HAVE AND IT'S BEEN AN

1559
01:04:22,560 --> 01:04:24,440
OUTSTANDING STORY AND A

1560
01:04:24,440 --> 01:04:25,440
PLAINTIFF FOR NIH TO PLAY A ROLE

1561
01:04:25,440 --> 01:04:27,360
IN SUPPORTING IT AND WE

1562
01:04:27,360 --> 01:04:28,560
APOLOGIES FOR THE INTENSITY OF

1563
01:04:28,560 --> 01:04:29,520
THE MEETINGS YOU HAD THIS

1564
01:04:29,520 --> 01:04:31,400
MORNING AND NOW YOU CAN REST AND

1565
01:04:31,400 --> 01:04:32,600
RELAX AND I THINK WE'VE GOT A

1566
01:04:32,600 --> 01:04:33,920
BAD ENOUGH TIME TO LET YOU SEE

1567
01:04:33,920 --> 01:04:38,880
THE FLORENCE MAHONEY MEMORIAL

1568
01:04:38,880 --> 01:04:39,360
GARDEN.

1569
01:04:39,360 --> 01:04:41,960
ON BEHALF OF ALL OF US, THANK

1570
01:04:41,960 --> 01:04:43,400
YOU FOR THE VISIT AND ALL THE

1571
01:04:43,400 --> 01:04:43,800
WORK THAT YOU DO.

1572
01:04:43,800 --> 01:04:44,960
>>THANK YOU, VERY MUCH.

1573
01:04:44,960 --> 01:04:55,120
EVERYBODY.