>>IT'S MY PLEASURE TO WELCOME
YOU TO FLORENCE MAHONY
BASED ON HER OUTSTANDING
GROUND-BREAKING WORK ON STUD'S
OF THE COLOMBIA YAN KINDRED WITH
AUTOSOMAL ALZHEIMER'S DISEASE.
THEY'RE IN MEMORY OF FLORENCE
MAHONEY.
SHE SPENT HER LIFE PROMOTING NIH
AND NATIONAL INSTITUTE ON AGING
UNTIL HER DEATH AT AGE OF 103
AND UP UNTIL THAT TIME, I WOULD
MEET WITH HER EACH YEAR AND SHE
WONDERED WHO WOULD GIVE THE
LECTURE AND SHE WANTED NO
NONSENSE.
ONE OF THE MOST CUTTING EDGE BUT
ALSO RIGOROUS SCIENTIST AND SHE
WOULD BE THRILLED TO SEE OUR
TRADITION BEING KEPT UP TODAY
SO, TO INTRODUCE YOU SHE BEGAN
HER CAREER WITH HER
UNDERGRADUATE EDUCATION AT THE
ANTI-OPENNIA WHERE THE KINDRED
HAS BECOME A FOCUS OF HER STUDY
AND HAS ORIGINATED AND SHE WENT
TO BOSTON UNIVERSITY FOR BOTH
HER MASTERS AND PH.D DEGREE IN
CLINICAL NEUROSCIENCE.
MOVED TO MASS GENERAL WHERE SHE
HAS NOW ADVANCED TO THE LEVEL OF
ASSOCIATE PROFESSOR IN THE
DEPARTMENT OF NEUROLOGY AND
PSYCHOLOGY.
SHE'S BEEN HONORED BY MULTIPLE,
INCLUDING THE NIH EARLY
INDEPENDENCE AWARD OF ONE WHICH
ENCOURAGES PEOPLE WITH HIGH
PROMISE, EARLY IN THEIR CAREER
TO MOVE FORWARD WITH
INDEPENDENCE AND A GREAT HONOR
IN DEED.
HONORS BY THE ALZHEIMER'S
ASSOCIATION AND MGH AND TODAY
WE'LL HAVE AN OPPORTUNITY TO
HEAR ABOUT HER ABOUT THIS GROUND
BREAKING WORK.
I ENCOURAGE YOU TO HAVE YOUR
QUESTIONS READY FOR HER AND
WE'LL BE BACK WITH THEM AT THE
END OF HER TALK.
[APPLAUSE]
>> THANK YOU FOR THE KIND
INTRODUCTION AND ALSO FOR THE
INVITATION TO PRESENT OUR WORK.
IT'S REALLY AN HONOR TO GIVE
THIS LECTURE AND FLORENCE
MAHONEY'S WORK SO THANK YOU FOR
THE OPPORTUNITY.
I'M GOING TO SHARE SOME OF THE
WORK WE'VE BEEN DOING WITH THE
COLOMBIA KINDRED AND IT'S A
DISEASE AND IT WAS MENTIONED
BEFORE SO MY NAME IS Dr.
QUIROZ FROM THE MASSACHUSETTS
GENERAL HOSPITAL.
I WEAR SEVERAL HATS.
BEFORE I MOVED TO THE COLOMBIA
YAN KINDRED IT WAS BASED ON A
CONVERSATION I HAD.
THIS MORNING, THANK YOU TO
EVERYBODY WHO GOT ON TIME TO
MEET WITH THIS MORNING AND IT'S
A BIG THANK YOU TO KIM FOR
ORGANIZING ALL THE LOGISTICS FOR
THIS MEETING AND I APPRECIATE
IT.
SO, I WILL HAVE THE MULTI
CULTURAL SCIENCE PROGRAM AND
THEY'RE GOING TO BE MENTIONED
THESE ARE IN THE PRESENTATION
BUT I WANT YOU TO MENTION THAT
I'M VERY STRONG AND VERY
COMMITTED TO INCREASING THE
PRESENTATION OF WOMEN AND OTHER
UNDER REPRESENTED MINORITIES
GROUPS IN RESEARCH AND SCIENCE
AND WE TRIED TO FOLLOW THE
CULTURAL DIVERSION PREVENTION
AND JUST LAST MONTH, WE WROTE
THIS PERSPECTIVE REVIEW PAPER SO
I INVITE YOU TO, IF YOU ARE
INTERESTED IN THIS TOPIC, TO
TAKE A LOOK AND LEARN MORE ABOUT
THE WORK WE'RE DOING AND
DIVERSITY AND CREASING DIVERSITY
IN CLINICAL CARE AND RESEARCH.
WITH THAT SAID, I'M GOING TO
MOVE TO THE TOPIC FOR TODAY.
IT'S GOING TO BE BASED ON THE
ALZHEIMER'S DISEASE.
SO FOR THE OUTLINE, WE'LL START
WITH AN OVERVIEW WHERE WE KNOW
ALZHEIMER'S DISEASE AND WE'RE
TALKING ABOUT SOME OF THE EARLY
THINGS WE HAVE WITH MUTATION
CARRIERS AND MOVING TO SOME OF
THE WORK WITH THE COLOMBIA
BOSTON YAN STUDY WITH THE
PATHOLOGY AND ALZHEIMER'S
DISEASE AND THEN DISCUSS WHAT WE
HAVE LEARNED ABOUT COGNITIVE
BIOMARKERS ESPECIALLY IN BRIEFLY
MENTIONED IN THE WORK THAT WE
HAVE DURING THE PAST FEW YEARS
WITH REMOTE AND THE BIO MACKERS
AND LASTLY SOME OF THE WORK WITH
THE COLBOS EXTREME IN RESILIENCE
IN THE KINDRED.
AND JUST TO MAKE SURE THAT
EVERYBODY -- I KNOW YOU ARE
FAMILIAR WITH THIS BUT JUST TO
MAKE SURE THAT EVERYBODY IS ON
THE SAME PAGE AS REMINDERS SO
THE MOST COMMON FORM OF
ALZHEIMER'S DISEASE IS ONSET
ALZHEIMER'S DISEASE THIS IS
EXPLAINS THE CASES.
USUALLY WE THEY WILL THEY HAVE A
SYMPTOMS OR THE AGE OF 65 AND
THERE ARE SOME IMPORTANT RACE
FACTORS, OLDER AGE ARE THE MOST
IMPORTANT ONE BUT FOLLOWED BY
FAMILY HISTORY AND ALSO WE KNOW
THAT THE MAIN RISK FACTOR IS
APOE4 AND THERE'S ANOTHER ONE WE
CALL FAMILIAR ALZHEIMER'S
DISEASE AND IT'S ONLY ON
MINORITY OF CASES AND IT'S
USUALLY EXPLAINED BY ALZHEIMER'S
MUTATIONS IN THREE MAIN GENES
THAT ARE PRESENTING.
ONE PRESENT IT WOULD GO AND APP
GENES AND DIFFERENT FROM THIS
ONSET ALZHEIMER'S DISEASE, IT'S
USUALLY DEVELOPED AND
ALZHEIMER'S DISEASE BEFORE THE
AGE OF 65 AND THIS MUTATIONS ARE
NEARLY HIGHLY PENETRANTS AND PED
THEY HAVE CLINICAL ONSET AND YOU
ARE FAMILIAR WITH THIS SO WE'RE
MOVING TO THE DEFINITION OF
ALZHEIMER'S.
THE LAST PHASE IS D DEMENTIA AND
THE CURRENT READINGS ARE
DEVELOPED BETWEEN WHEN THEY
ALREADY HAVE SYMPTOMS AND ALL
THE WORK THAT WE HAVE DID NOT
DOING IN THE PAST SEVERAL YEARS
HAS BEEN TRYING TO IDENTIFY THE
CLINICAL STAGE AND ONE OF THE
GOALS ORIENTED TO FINDING THIS
IS TO BE ABLE TO DELAY THE
CLINICAL ONSET AND OF COURSE IN
THE FUTURE BE ABLE TO PREVENT
ALZHEIMER'S AND DEMENTIA BOTH
TOGETHER.
ONE OF THE GOALS OF THIS
PREVENTION WERE IS THE CLINICAL
DETECTION OF ALZHEIMER'S IS TO
ACTUALLY BE ABLE TO INITIATE
TREATMENT AS EARLY AS POSSIBLE
SO THEY HAVE THE BEST POSSIBLE
OUTCOME.
AND TOGETHER WITH THE
TREATMENTS, WE ALSO HAVE THE
POSSIBILITY OF BEING ABLE TO
PREVENT ALZHEIMER'S DISEASE ALL
TOGETHER IN THE FUTURE.
ONE WAY THAT WE HAVE BEEN USING
TO ACTUALLY DETECT ALZHEIMER'S
DISEASE AS EARLY AS POSSIBLE IS
THROUGH BY BIOMARKERS AND AS YOU
MAY KNOW AS WELL SO BIOMARKERS
GIVE YOU THE CHANCE TO DETECT
ALZHEIMER'S DISEASE OR ANY
DISEASE AND GIVE YOU A CHANCE TO
STAY THE DISEASE AND MONITOR THE
DISEASE AND CLINICAL TRIALS GIVE
YOU A CHANCE TO MONITOR THE
RESPONSE TO TREATMENTS.
THERE ARE SEVERAL BIOMARKERS
VALIDATION AND HERE I'M SHOWING
SOME OF THE BIOMARKERS THAT WE
ARE CURRENTLY PURSUING AT SOME
POINT AND BIOMARKERS USING IMAGE
ARE FOR ATROPHY, AND TAU, AND
BIOMARKERS THAT ARE DEVELOPED
FOR NEURO INFLAMMATION AND WHEN
YOU TALK WITH BIOMARKERS, THERE
ARE TWO WAYS TO GO ABOUT
BIOMARKERS.
ONE, YOU CAN HAVE THOSE THAT ARE
AT INCREASED RISK TO DEVELOP
ALZHEIMER'S IN THIS CASE LATE
ONSET ALZHEIMER'S.
OR YOU CAN ALSO GO ABOUT
ALZHEIMER'S DISEASE AND AS YOU
ALREADY KNOW BY THE TALK ON THE
PRESENTATIONS, THIS IS THE WAY
THAT WE HAVE BEEN WORKING OUT
THESE BIOMARKERS.
THIS IS SOMETHING THAT WE HAVE
BEEN DOING FOR SEVERAL YEARS SO
IT WAS SOMETHING THAT FRANCIS,
THE GUY HERE IN THE PICTURE,
STARTED DOING 30 YEARS IN
COLOMBIA.
IN COLOMBIA WE HAVE FAMILIES WE
HAVE MANY DISEASE ALZHEIMER'S
AND HUNTINGTON AND CADASIL AND I
JOIN HIS GROUP WHEN I WAS IN
COLLEGE SO FOR ME, A LITTLE OVER
20 YEARS AND SINCE THEN, I HAVE
BEEN WORKING WITH HIM IN THIS
PROJECT CHARACTERIZING THESE
FAMILIES.
SO MY MAIN CONTRIBUTION TO THE
WORK OF THE GROUP IN COLOMBIA
HAS BEEN MOSTLY FOR BIOMARKERS.
HELPING TO GET THE FAMILIES
READY SO JUST REMIND YOU A
LITTLE BIT, TELL YOU A LITTLE
BIT ABOUT THESE FAMILIES THAT WE
FOLLOW, SO THE ONES WITH
ALZHEIMER'S DISEASE, WE HAVE THE
WORLD'S LARGEST EXTENDED FAMILY
WITH A SINGLE GENETIC MUTATION
FOR EARLY ALZHEIMER'S DISEASE
AND WE HAVE A LITTLE BIT OVER
6,000 INDIVIDUALS THAT CARRY A
SINGLE DNA MUTATION AND THIS IS
THE E288 MUTATION.
AND INDIVIDUALS THAT CARRY THIS
MUTATION THEY DEVELOP COGNITIVE
IMPAIRMENT ABOUT THE AGE OF 44
AND DEMENTIA AT THE AGE OF 49.
THERE ARE SEVERAL SIMILARITIES
BETWEEN THESE FORM OF THE
DISEASE AND THE MOST COMMON FORM
OF THE DISEASE AT LEAST IS THE
LATE ONSET AND IT'S BETWEEN THE
TWO TYPES.
THERE'S A OPPORTUNITY TO SAY
THESE FAMILIES GIVE YOU AN
OPPORTUNITY TO SEW INDIVIDUALS
THAT ARE DESTIN TO DEVELOP
ALZHEIMER'S AND DEMENTIA IN THE
FUTURE BUT WITH SEVERAL YEARS OR
DECADES BEFORE THEY HAVE ANY
SYMPTOMS, SO WE HAVE A WINDOW OF
OPPORTUNITY TO CHARACTERIZE SOME
OF THE CLINICAL CHANGES RELATED
TO ALZHEIMER'S DISEASE.
AND THIS IS ONE OF THE FIRST
QUESTIONS THAT I HAVE BEEN IN
ANSWERING AND WORKING ON THAT SO
WHAT ARE THE EARLY BIOLOGICAL
AND PHYSIOLOGICAL CHANGES
ASSOCIATED WITH THE POSITION TO
ALZHEIMER'S.
AND TO START ANSWERING THAT
QUESTION, THE FIRST SET OF THE
STUDIES WE DID WAS USING A
FUNCTION MRI.
THIS IS SOME OF THE WORK THAT I
DID WHEN I WAS A PH.D STUDENT, I
STUDENTS MRI TO DECIDE BRAIN ACT
EVACUAACTIVATION WHEN THE BRAIN
CARRIERS ARE THE SIBLINGS AND IT
LEARNING NEW FACE NAMES WHEN
THEY WERE IN THIS AND THE FIRST
WAS THIS ONE IT WAS OLDER
CARRIERS AND COLDER THAN 25.
WHEN WE COMPARED THE LEARNING
DURING THE YOUNGER AND THE
REPEATED NAMES WE FOUND THE
CARRIERS ACTUAL LOW HAD HYPO CAM
PA ACTIVATION COMPARED TO THE
NON CARRIERS AND IT WAS ALREADY
TELLING US THEY HAVE SOME BRAIN
I AM NORMALITIES IN BRAIN
FUNCTION OR IN THIS CASE
LEARNING FACE NAMES.
THEN I DECIDED TO GO YOUNGER SO
WE WENT TO 18-25 AND WE DID THE
SAME TASK.
THEY WERE USING THE SAME FACE
NAME TASK AND THEN WE ACTUALLY
SAW THAT IN ADDITION INFORM THIS
HYPER ACTIVATION THEY HAVE HYPER
ACTIVATION IN OTHER REGIONS AND
OTHER REGIONS OF THE GAME SO
PRETTY MUCH THERE WAS STILL SO
ABNORMALITIES IN THE CARRIERS
COMPARED TO A NON CARRIER AND
THEN, I WENT EVEN YOUNGER AND
INCREASED IN CHILDREN THIS CASE
INDIVIDUALS FROM 9 YEARS TO 18
YEARS, AND THEN THE FIRST THING
WE FOUND IT WAS THERE WAS NO
DIFFERENCE IN THE TEMPORAL LOBE
BETWEEN CARRIERS AND NON
CARRIERS AND WE SAW THIS TYPIER
ACTIVATION IN THE CARRIERS
COMPARED TO A NON-CARRIER AND WE
CALL HERE LESS ACTIVATION OF
REGIONS AND WE DON'T EXPECT THIS
ACTIVATION DURING THIS TASK SO
THIS THREE EXPERIMENTS TELLING
US THERE WERE ABNORMALITIES IN
THE CARRIERS SEVERAL YEARS
BEFORE THEY HAVE ANY KIND OF
SYMPTOMS.
THEN I STARTED LOOKING AT
STRUCTURE AND THE NEXT WAS
CORTICAL THICKNESS AND THE OLDER
CARRIERS AND WE FOUND THAT THE
CARRIERS COMPARED TO THE NON
CARRIERS, THEY ACTUALLY HAVE
CORTEX IN THE REGIONS AND FEW
YEARS BEFORE SYMPTOMS AND THEN I
USED ERP THAT IS POTENTIAL SO
BASED ON EEG IN THIS CASE AND
THE CARRIERS ALSO HAVE
ABNORMALITIES IN EXTERIOR
REGIONS WHEN THEY WERE LEARNING
COMPARED TO THE NON CARRIERS.
SO THIS FIVE EXPERIMENTS ALL
TOGETHER PROVIDE SOME OF THE
FIRST AREAS TO BE BRAIN CHANGES
IN COGNITIVELY TO INDIVIDUALS
MANY YEARS BEFORE CLINICAL
ONSET.
AFTER ALL THIS IS DONE, WE START
AND WE USE ALL BIOMARKERS
INCLUDING BIOMARKERS IN CSF AND
THE FIRST STUDY WE DID FOR AM
LLOYD AND PUTTING ALL THE
MARKERS TOGETHER, IN THIS AGE
RELATED TRAJECTORY ACTUALLY
OBSERVED THAT THE FIRST
ABNORMALITIES IN THIS INDIVIDUAL
ARE SHOWED BEFORE, THE EARLIEST
ABNORMALITIES THAT WERE SEEN
WERE CHANGES IN AMALIOI AND AS
EARLY AS IN THE EARLY 20s.
SO, ONE OF THE FIRST QUESTIONS
YOU WILL SEE THAT IN THIS
PRESENTATION I HAVE MORE
QUESTIONS THAN ANSWERS, ONE OF
THE FIRST QUESTIONS THAT I HAVE
OF THIS IS PRETTY MUCH NOW THAT
WE HAVE EVIDENCE OF THIS
ABNORMALITIES, SO WE KNOW THERE
ARE ABNORMALITIES IN BRAIN
FUNCTION BUT WHAT ARE ACTUALLY
THE EARLIEST ABNORMALITIES AND
IT'S ACTUALLY WITH ANOTHER
COUPLE OF QUESTIONS THAT I STILL
DON'T HAVE THE ANSWER AND IT'S
LIKE ARE THERE ANY NEURO
DEVELOPMENTAL DIFFERENCES
BETWEEN THE CARRIERS AND THE NON
CARRIERS?
I MEAN IN CASE THERE ARE NEURO
DEVELOPMENTAL CHANGES DUE TO
THIS MUTATION, ARE THESE
CONTRIBUTING TO FUTURE COGNITIVE
DECLINE IN THE CARRIERS AND THE
ANSWER TO THIS QUESTION WHICH I
STILL DON'T HAVE THE ANSWER.
I WANT TO BRING YOUR ATTENTION
BACK TO THE CHILDREN STUDY WHEN
IN ADDITION TO THE ABNORMAL
ACTIVITY DURING TASK RELATED TO
THE MRI WE FOUND ABNORMALITIES
AND RESTING STATE NETWORK AS
SEEN HERE AND WE FOUND INCREASED
CONNECTIVITY BETWEEN THE POSTER
YEAR REGIONS AND THE TEMPORAL
AND WE HAVE GRAY MATTER VOLUME
IN TEMPORAL REGIONS IN THE
CARRIERS COMPARED TO NON
CARRIERS.
EVEN A 90-YEARS-OLD, THE
YOUNGEST ONES THAT WE HAVE, WE
ARE SEEING THESE DEVELOPMENTAL
CHANGES IN THE CARRIERS COMPARED
TO FINANON CARRIERS.
HAVING ALL THE IMAGING WE HAVE
WITH THIS INDIVIDUALS, SO
TOGETHER ONE OF MY PH.D STUDENTS
ACTUALLY PUT ALL THIS DATA
TOGETHER AND WE STARTED LOOKING
AT THE LIFESPAN AND THIS IS ONE
OF THE FIRST ATTEMPTS TO LOOK AT
DATA ALL TOGETHER AND WE PUT
TOGETHER 200MRIs THAT WE HAVE
THAT EVERYBODY THAT I SHOWED
BEFORE AND THIS IS KIND OF LIKE
WHAT WE FOUND IS VERY
INTERESTING, WE FOUND THAT
THEY'VE TAKEN IT'S THE FIRST
MEASURE WE ENCLOUD HERE IT'S
FLUCTUATING ALONG THE LIFESPAN
AND WE FOUND TWO POINTS THAT WAS
CLEAR AT THE AGE OF 17 AND ONE
AT THE AGE OF 32 WHEN THEY
STARTED DECLINING UNTIL THEY
STARTED DEVELOPING MCI AND
DEMENTIA.
I WAS STILL VERY INTRIGUED AND I
WAS GOING ON HERE BEFORE THE AGE
OF 17.
WE WENT AND TOGETHER WITH MY
PH.D STUDENT AND ANOTHER PH.D
STUDENT, WE WENT INTO THE
COGNITION AND WE COLLECTED DATA
IN THIS CASE IN OVER 1,000
CHILDREN FROM THE KINDRED, USING
THIS MEASURE THAT IS ONE OF THE
FIRST MEASURES AVAILABLE AND WE
DIDN'T FIND DIFFERENCE BETWEEN
THE CARRIERS AND THE NON
CARRIERS BUT WHEN WE STARTED
LOOKING AT THE DATA, WE ACTUALLY
FOUND SEX DIFFERENCES IN
COGNITIVE ABILITIES BETWEEN THE
CHILDREN IN THE WAY THAT THEY
ACTUALLY -- THE BOYS, WITH THE
MUTATION, THEY HAVE DECREASED
WORKING MEMORIES COMPARED TO THE
GIRLS WITH THE MUTATION AND I
KNOW IT'S COMPARED TO THE
MUTATION.
WE PRETTY MUCH SUGGEST SEX IS A
GENETIC RISK IN THESE EARLY LIFE
COMMUNITY PERFORMANCE AND FOR ME
IT'S VERY INTERESTING AND IT'S
TELLING US THERE'S SOMETHING IN
THE DEVELOPMENT THAT NEEDS TO BE
FURTHER EXPLORED AND MORE THAN
THAT, THIS INCREASED RISK OF
FUTURE COGNITIVE ABILITY AND
ESPECIALLY THE ONES IN THE BOYS,
MAY HAVE IMPORTANT IMPLICATIONS
FOR THESE CHILDREN EVEN WHEN WE
ARE THINKING ABOUT LEARNING AND
ACHIEVEMENT AND EVEN IN THE
FUTURE MAY BE RELATED WITH THE
SEX DIFFERENCES THAT ARE SEEN.
>> WE DIDN'T HAVE TAU PATHOLOGY
AND IN COLOMBIA WE DIDN'T HAVE
THAT TECHNOLOGY AND IT'S
SOMETHING THAT I WAS MISSING
LIKE THE SAME WE HAVE HERE AND
WE HAVE CSS AND WE HAVE MRI BUT
WE DON'T HAVE A PET SO FOR THIS
I THOUGHT IT WAS VERY IMPORTANT
TO ACTUALLY HAVE THE PIECE OF
THE PUZZLE TO UNDERSTAND HOW THE
TAU PATHOLOGY IN RELATION TO
PATH OLE GOUGH FATE IN THE
TRAJECTORY OF THE DISEASE SO IN
2014, Dr. ROSE MENTIONED THIS
AT BEGINNING, I APPLIED AND
RECEIVED ONE OF THE DP5 GRANTS
AND AS PART OF THE DP5, ACTUALLY
PROPOSE TO BRING THE COLUMBIANS
TO BOSTON AS PART OF WHAT I
CALLED COLBOS AND IT'S
COLOMBIA-BOSTON AND I WAS
BROUGHT INTO BOSTON TO HAVE THE
NEUROIMAGING DONE IT WAS NOT
AVAILABLE IN COLOMBIA AND TRYING
TO ANSWER THE QUESTION, WHAT
HAPPENED WITH TAU PATH PATHOLON
THE BRAIN AND OTHER BIOMARKERS.
WHAT WE HAVE LEARNED FROM THE
COLBOS WE HAVE 81 INDIVIDUALS
THAT CAME FOR BASELINE
EXAMINATIONS AND SO WE PUT IN
THE FIRST REPORT THAT THE
CARRIERS ACTUALLY HAVE AMELO
POSITIVITY AS EARLY AS THEY ARE
28-YEARS-OLD AND WE ALSO LEARNED
THAT THEY HAVE INCREASED TAU
PATHOLOGY COMPARED TO THE NON
CARRIERS IN THE LATE 30s AND
NOW WE KNOW THAT IT'S AS EARLY
AS THEY ARE 36, A FEW YEARS
BEFORE THE CLINICAL ONSET AND WE
ALSO NOW KNOW THE ACCUMULATION
OR TAU PATHOLOGY BEGINS AND THE
CORTEX AND IT'S EXPRESSED FROM
THE CORTEX TO OTHER REGIONS.
WE ALSO LEARNED THAT INCREASED
LAYERS OF TAU WOULD ONLY SEEN IN
THE SETTING OF STUB TAN SHALL
OPPOSITION AND ALL INDIVIDUALS
THAT ACTUAL WILL HE HAVE HIGH
LAYERS OF TAU ALREADY HAD HIGH
LEVELS OF AMYLOID AND IT WAS
CORRALLATED WITH DECLINE AND WE
KNOW AMYLOID WITH DECLINE THAT
AMYLOID AND THE OTHER THINGS IN
THE PICTURE, WHEN THEY LOOK BY
COGNITIVE IMPAIRMENT, TAU
PATHOLOGY IS SPREAD IN THE NEO
CORTEX IS (INAUDIBLE).
JUST RECENTLY AND THIS IS
SOMETHING THAT MY COLLEAGUES
WERE LEADING THIS EFFORT SO WE
STARTED GOING BACK TO THE
CONNECTIVITY, WHICH I'M STILL
VERY INTO THE COGNITIVE TEE SO
WE TRIED TO HAVE THE ASSOCIATION
WITH TAU PATHOLOGY AND BRAIN
CONNECTIVITY AND USING THE
APPROACH OF USING SEEING IF
THERE WAS ANY ASSOCIATIONS OF
TAU PATHOLOGY AND THE FUNCTION
OF SEGREGATION AND INTEGRATION
IN THE BRAIN NETWORKS AND WE
ACTUALLY FOUND THE MUTATION
CARRIERS HAVE ASKING ROW GAYS
AND INTEGRATION IN THE FORMAL
NETWORKS AS YOU SEE HERE AND WE
TOOK OUT THE ASSOCIATION WITH
TAU WE FOUND THE GREATER TAU
PATHOLOGY WAS ACTUALLY
ASSOCIATED WITH LOWER
SEGREGATION AND INTERNET GRA
TIVE AND I'M SORRY.
PRETTY MUCH HERE IN THIS FIRST
REPORT WE'RE SHOW THAT EVEN
THOSE LEVELS OF TAU PATHOLOGY,
WHICH IN THE SAMPLE, THEY'RE
VERY INSIM LEVELS TO THEY'RE
STARTING IN THE BRAINS AND THOSE
LEVELS ARE ALREADY IN PART IN
THE BRAIN FUNCTION ORGANIZATION
SEVERAL YEARS BEFORE THEY HAVE
IMPAIRMENT.
ALL OF THIS IS I DIDN'T SHOW
THIS DESCRIPTION BUT THEY
IMPAIRED AND WE ONLY HAVE SEVEN
WITH COGNITIVE IMPAIRMENT.
WE STARTED AND THE BIOMARKER
STARTED AND AS PART OF THE
LONGITUDINAL MARKER ASIDE, WE
INVITED INDIVIDUALS TO COME BACK
FOR FOLLOW-UP, EXAMINATIONS AND
THEY WERE COMING BACK AFTER 18
TO 24 HOURS AND THIS PART WAS
RUNNING VERY SMOOTHLY UNTIL I'M
GOING TO SHOW YOU THE ONES THAT
WE COLLECTED BEFORE AND SO FAR
WE HAVE 35 THAT HAVE BEEN ABLE
TO COME BACK FOR THE THREE TIMES
AND AS PART OF THE FOLLOW-UP
THIS IS SOMETHING THAT WAS
SLOWED WE FOUND THAT CARRIERS
COMPARED TO THE NON CARRIERS
HAVE GREATER TAU PATHOLOGY AS
YOU CAN SEE HERE AND IT WAS VERY
INTERESTING AND I FOUND VERY
INTERESTING AND IT'S SOMETHING
WITH MORE WE HAVE BEEN ABLE TO
CONFIRM HERE WE HAVE THE
CARRIERS AND THEY'RE IN BLUE AND
THE FEW THAT WE HAVE THERE FOR
IMPAIR AND THE CONTROLS AND YOU
CAN ACTUALLY SEE THAT THE
UNIMPAIRED ACCUMULATION OR AM
LLOYD APPEARS TO BE A STEADY
PROCESS AND BEGINNING AS EARLY
AS 20 YEARS PRIOR TO THE
DEMENTIA ONSET AND HERE IS
AMYLOID AND THIS IS H AND YOU
CAN SHOW TAU COMPARED TO ACE YOU
CAN SEE IN CONTRAST, TAU
PATHOLOGY IS VERY RAPID AND
WIDESPREAD IN THE TAU AND YOU
CAN SEE IT ACTUALLY, NOTHING
MUCH HAPPENS IN THE EARLY 30s
BUT AS SOON AS THEY GET CLOSER
YOU CAN SEE THESE RAPID INCREASE
OR TAU AND NOW THAT WE HAVE MORE
AND THE PATTERN IS VERY SIMILAR
AS WELL.
TO TAU AND AMYLOID CHANGES THE
MEASURES ARE VERY CORRELATED AND
TAU BASELINE AND THE CHANGES ARE
ALSO LINKED TO MEMORY DECLINE
AND MORE LINKED TO MEMORY
DECLINE THAN AMYLOID.
WITH ALL THIS DATA YOU CAN SEE
WE HAVE TRIED TO MAKE A
DIFFERENCE WITH DIFFERENT
QUESTIONS AND ALL ARE USED TO
IMPROVE BIO MARKERS AND
UNDERSTAND AND PROTECT AND RAISE
FACTORS FOR THOSE RELATED
COMMUNITY DELINE AND DEMENTIA
USING THIS DISEASE AND WE ARE IN
THE DEX SISS IN THIS FOR
INSTANCE AND ALSO UNDERSTANDING
THE LEAD AND PHYSICAL ACTIVITIES
AND CHRONIC STRESS AND AND THE
SIGN THAT THE FACTORS AND OF
COURSE OTHER FACTORS AS WELL AND
WHY HAVE TIME TO GO THROUGH ALL
THIS SLIDES BUT I'LL HIGHLIGHT A
FEW OF THEM JUST FOR YOU TO GIVE
ATTENTION TO WHAT WE DO TO I'M
GOING TO START WITH SOME OF THE
APPLICATIONS OF THE WORK THAT WE
HAVE BEEN DOING AND STARTING
WITH EARLY DIAGNOSIS.
OF COGNITIVE DECLINE AND
DEMENTIA AND EVERYTHING WE DO
WITH THE COLUMBIAN KINDRED WE DO
IN SPANISH AND WE VALIDATE AND
DEVELOP SOME OF THE MEASURES FOR
A TESTING IN SPANISH SPEAKERS
AND THIS IS ONE EXAMPLE SO THE
FIRST THING ASSOCIATED WITH
MEMBER ROW EXERCISE FACE NAME,
WAS ONE THAT WAS ACTUALLY
SHOWING TO BE SENSITIVE TO
CLINICAL ALZHEIMER'S DISEASE AND
WE ACTUALLY CREATED THE LATINO
AMERICAN VERSION VALIDATED
VERSION IN THE COLOMBIA SAMPLE
AND CREATING NORMS FOR CLINICAL
USE.
THERE IS THIS PAPER AND FOR
CLINICAL USE WE ACTUALLY USE IT
IN COLBOS TO TEST IT INTACT
INDIVIDUALS TO SEE IF THE
MEASURE WAS ACTUALLY ABLE TO
DETECT A CARRIER FROM
NON-CARRIERS AND WHETHER IT WAS
CORRELATED WITH TAU POTHOLOGY.
THIS IS SOME OF THE WORK ONE OF
MY DOCTORS WAS ACTUALLY LEADING.
THIS IS HOW THE TASK LOOKS.
THE TASK IS AVAILABLE AS PART OF
THE NIH TOOLBOX SO WE HAVE THE
LEARN PHASE AND THEY HAD TO
IDENTIFY AND RECOGNIZE THE FACE
AND THE LETTER AND THE NAME.
SO WHAT WE ACTUALLY FOUND WITH
THE COLBOS DATA IT ENCLOUDS ONLY
ONE THAT ARE CONSIDERED
COGNITIVELY INTACT.
THEY DON'T HAVE CONCERNS OF
MEMBER ROW.
AS CLEAN AS IT GETS.
AND WE ACTUALLY WERE ABLE TO USE
THIS TEST TO SHOW THAT ONLY A
PERFORMANCE IN THE TASK, AS ABLE
TO DISTINGUISH CARRIERS FROM NON
CARRIERS.
THEY DEFINE THE CARRIERS FROM
NON CARRIERS EVEN WITHIN THE
NORMAL RANGE OF PERFORMANCE.
WE THEN LOOKED AT THE
CORRELATIONS WITH PATHOLOGY AND
HERE AND SHOW THE PERFORMANCE
AND IMMUNO PATHOLOGY AND THE
WORST PERFORMANCE IN THE TEST
WAS CORRELATED WITH GREATER
AMYLOID AND THE SAME IN
INDIVIDUALS WITH NO AND
COGNITIVE CONCERNS OR COGNITIVE
DECLINE AND THEN WE DID THE SAME
WITH INTER RYAN A AND FIRST WAS
ASSOCIATED AND WE WERE WITH
GREATER LEVELS OF PATHOLOGY AS
WELL AND THEN AS THE ANALYSIS WE
USED THE ASSOCIATIONS WITH
PERFORMANCE AND THE TAU
PATHOLOGY HERE AND AMYLOID HERE
AND THE REGIONS OF THE BRAIN
WERE MORE WITH PERFORMANCE AND
IN THE TAU IN PARTICULAR AND
THEN THE ONES WE KNOW THAT ARE
SENSITIVE TO EARLY ACCUMULATION
OF PATHOLOGY AS WELL.
ONCE AGAIN, IN INDIVIDUALS WITH
NO COGNITIVE SYMPTOMS SO IT'S A
PROMISING TASK AND WE CONTINUE
TO USE IT IN THE STUDY AS WELL.
WITH TO THE REMOTE TESTING, WE
DID TOO SO I ACTUALLY CREATED
THE COVID REMOTE AND I WAS
PRETTY MUCH A STUDY IN COLOMBIA.
WHEN WE RECRUITED A COHORT OR
INDIVIDUALS AND PRETTY MUCH WERE
GOING TO AND UNDER WIND A REMOTE
TESTING AND BLOOD TESTING EITHER
IN THE COMPUTER OR IN THE
SMARTPHONE SO WE USED THE
OPPORTUNITY TO ACTUALLY VALIDATE
SOME OF THE MEASURES THAT WERE
DESIGNED FOR REMOTE TESTING AND
WE HAD SO FAR FOUR MEASURES THAT
ARE NOVEL MEASURES AT A
DIFFERENT STAGES OR PILOTING AND
I'M GOING TO SHARE ONE THAT IS
MORE ADVANCED AND THE MEASURES
THAT WE HAVE IN DIFFERENT STEPS
AND THEY ARE MULTI CULTURAL,
MULTI LINGUAL SO RIGHT NOW WE
HAVE IN ENGLISH, SPANISH AND
KOREAN AND WE'RE DEVELOPING ONE
IN PORTUGUESE AS WELL.
SO THE IDEA IS TO HAVE THIS
AVAILABLE IN THE FUTURE FOR
ANYONE THAT WANTS ACCESS TO
THESE MEASURES.
SO I WANTED TO SHARE WITH YOU AS
AN EXAMPLE IS MEMORY RELATED OR
JUST DEMONSTRATED AND HERE IS
ONE MY PH.D STUDENT WAS LEADING
THIS EFFORT AND WE HAVE OBJECTS
RELATED VERSUS THESE RELATED AND
THEY HAVE TO LEARN THESE BASED
ON THE DELAYED EXAMPLE OF THE
TEST AND THEY HAVE TO JUST SAY
THEY MATCH OR NO MATCH AND AFTER
A FEW SECONDS DELAY AND WHAT WE
FOUND IS THIS IS INCLUDING ONLY
COMPLETED THE TASK IN THE
COMPUTER SO THEY WERE GIVEN THE
OPTION OF COMPLETING IT IN THE
COMPUTER OR THE SMARTPHONE AND
HERE FOR THIS ANALYSIS WE ONLY
INCLUDED THE ONES COMPLETED IN
THE COMPUTER SO WE HAVE 35 THAT
WERE CARRIERS AND 23 THAT WERE
NON CARRIERS AND FIVE THAT WERE
MCI AND WHAT WE'RE SEEING WITH
THE PERFORMANCE IS THE TOTAL
PERFORMANCE WAS THE SAME AND IT
WAS DIFFERENT EVEN WITHIN THE
NORMAL RANGE AND ALSO BETWEEN
THE TWO CONDITIONS THE RELATED
WERE THOSE THAT WERE
CONTRIBUTING TO THE DIFFERENCE
BETWEEN THE CARRIERS AND THE NON
CARRIERS.
AND WE LOOK AT THE TWO
CONDITIONS THAT WERE FOUR ITEMS
VERSUS SIX ITEMS, THE ONLY FOUR
ITEMS FOR INSTANCE WAS THE ONE
THAT WAS A DISTINGUISHED IN THE
CARRIERS COMPARED TO UNIMPAIRED
VERSUS THE KNOWN CARRIERS, THE
MCI THEY PERFORMED LOWER IN
EVERYTHING.
BUT THIS IS JUST AN EXAMPLE TO
SHOW YOU THAT THE OPPORTUNITY
FOR DESIGNING MEASURES THAT CAN
ACTUALLY DETECTOR BE MORE
SENSITIVE FOR A CLINICAL AND
SUBSIDAL CHANGES TO TAKE
INDIVIDUALS THAT ARE GOING TO BE
DEVELOPING COGNITIVE DECLINE IN
THE FUTURE AND INSTEAD OF USING
THE SAME MEASURES THAT WE HAVE
TRADITIONALLY USED TO IDENTIFY
WITH MICHAEL AND DEMENTIA.
SO THE OTHER POINT I WANTED TO
MENTION HERE IS THE SAME IN THIS
PART OF THESE EARLY DETECTION,
AS MANY IN THE FIELDS SO WE ALSO
HAVE TAKEN A LOOK AT BLOOD
MARKERS AND THIS IS SOMETHING
THAT IN THE PAST, LIKE THEY HAVE
COLLECTED BLOOD SAMPLES IN
SEVERAL INDIVIDUALS SO WE
STARTED LOOKING AT DATA
COLLECTED IN THE KINDRED SO IF
THE FIRST TWO PAPERS WE HAVE
THAT WE PUBLISHED TWO YEARS AGO
NOW, WE LOOK IN THE FIELD AND
ONE THAT ARE MARKERS IN THE
NEWER GENERATION AND ALSO THE P
TAU TO 17 IS ONE OF THE MARKERS
SO YEAH, OR P TAU AND IF THE
FIRST AND OR 2,000 INDIVIDUALS,
2,000 SAMPLES FROM THE KINDRED
AND WE SHOWED IS THAT THE MARKER
WAS ABLE TO DISTINGUISHED
CARRIERS BY THE AGE OF 20 AND IT
WAS TRUE FOR THE P TAU SO THEY
DISTINGUISHED CARRIERS AND NO
CARRIERS LIKE IN THE AGE OF 20
AND HERE I SHOW YOU WHEN WE
ACTUALLY PUT TOGETHER THE
CARRIERS FROM THE NON CARRIERS,
IT SEEMS LIKE THE P TAU WAS A
LITTLE BIT MORE SENSITIVE FOR
THE EARLIER CHANGES AND THAN THE
SO DISTINGUISH EARLY TO EARLY
THAN THE NON CARRIERS AND HAVING
THIS OPPORTUNITY TO HAVE THIS
DATA FROM BIOMARKERS, IT OPENS
ALSO A WINDOW FOR A LOT OF
OPPORTUNITIES IN TERMS OF
INCREASING ACCESS, INDIVIDUALS,
FOR INDIVIDUALS THAT DON'T HAVE
ACCESS FOR INSTANCE IN THIS CASE
TO GET TAU IMAGING OR AMYLOID
IMAGING AND SO FAR.
ONE OF THE OTHER QUESTIONS THAT
WE HAVE HERE, AND IT'S SOMETHING
THAT WE'RE SEEING A WORK IN
PROGRESS, LITTLE IS KNOWN ABOUT
THIS ASSOCIATION BETWEEN FOR
INSTANCE MARKERS OF PLASMA AND
MEASURES OF TAU AND ESPECIALLY
WHEN YOU ARE THINKING ABOUT
LONGER INTERVALS RIGHT IT'S
SOMETHING WE CAN PREDICT AND USE
ONE TO PREDICT CHANGES IN THE
OTHER ONE WHEN IT'S A LONGER
INTERVAL OF TIME SO SINCE WE
HAVE SOME DATA FROM TAU
PATHOLOGY, WE USE THE ONES THAT
HAVE PATHOLOGY AND A LOCK AT
ONES THAT HAVE THESE SAMPLES IN
P TAU IN THIS PAPER THAT WE JUST
SHOWED YOU AND AS THE QUESTION
IS PLASMA TAU, IT PREDICTS
LEVELS OF TAU PATHOLOGY AND
COMMUNITY PERFORMANCE AND I'M
GOING TO SPEND MORE DETAILS WHAT
WE DID.
SO THIS IS INDIVIDUALS THAT HAVE
PLASMA TAU IN THE SLIDE I JUST
SHOWED YOU AND THEN, ABOUT EIGHT
YEARS LATER, THEY CAME TO AND
THEY HAVE TAU AND WE USED THIS
OPPORTUNITIES TO TEST IF THESE
LEVELS PLASMA THAT THEY GET
WHERE WE CALL PACE BASELINE
WOULD HELP US PR PREDICT EIGHT
YEARS LATER.
WE HAVE 24 CARRIERS AND 20 THAT
WHY NON CARRIERS SO THIS IS
PRETTY MUCH THE SIDE THAT WE'RE
DOING NOW.
WE LOCK AT ONLY WITH 24 CARRIERS
HOW BEAUTIFUL THIS LOOKS.
SO, FIRST WE REPLICATE THAT
CARRIERS ACTUALLY HAVE HIGHER
LEVELS OF PET TAU 17 COMPARED TO
THE PLASMA P-TAU IS CORRELATED
WITH OLDER AGE.
THEY LOOK AT COGNITION AND HERE
THEY'RE ONLY LOOKING AND ONLY
SHOWING ONE TEST BUT IT'S PRETTY
MUCH ACROSS ALL THE DIFFERENT
COMMUNITY MEASURES LIKE ACTUALLY
P-TAU IS RECOGNITION ACROSS ALL
THE DIFFERENT THAT WE HAVE AND
ALMOST EIGHT YEARS LATER, AND
THEN IT ACTUALLY LOCKS AT PATH
PATHOLOGY AND THEY HAVE GREATER
PATHOLOGY IN AMYLOID AND ALSO IN
TAU AND HERE THEY'RE ONLY
SHOWING THE FIRST ONE THAT WE
SEE CHANGES BUT IT'S NOT ONLY
ASSOCIATED WITH LEVELS OF
ASSOCIATED WITH THE AND
PRECENMEUS AND IN THE CARRIERS
AND THE SAME ALMOST EIGHT YEARS
LATER, THIS IS STILL PREDICTING
THESE MEASURES.
WE RUN SOME EXPLORATORY ANALYSIS
AND WITH ALL THE CARRIERS YOU
CAN SEE ESPECIALLY WITH TAU.
TAU-PET THE TEMPORAL REGIONS AND
SINCE WE ARE HIGHLY CORRELATED
IS AND THESE ARE ALL THE
CORRECTIONS WE USE AND WITH
THESE CORRECTIONS WE TAKE A LOOK
ONLY THE IMPAIRED CARRIERS THE
LOBE REGIONS AND THE IT'S ALMOST
STILL THERE EIGHT YEARS AFTER
AND SO THIS IS UNBIASED BUT I
THINK THIS IS VERY BEAUTIFUL.
SO, BASELINE LAYERS OF PLASMA
P-TAU IS LEVELS OF AMYLOID AND
FUTURE MEMORY PERFORMANCE IN THE
CARRIERS AND THESE RESULTS ARE
VERY PRELIMINARY BECAUSE THERE'S
SOME PRECISE IS NOT THAT BIG BUT
THEY PROVIDE SUPPORT FOR PLASMA,
T-TAU AND DIAGNOSTIC MARKER OR
E280 COGNITION AND LEADING FROM
AND TRIALS AS I WAS SAYING, A
POSSIBILITY OF HAVING BLOOD
BIOMARKERS TO INCREASE ACCESS TO
EARLY DETECTION OF ALZHEIMER'S
DISEASE OR AT LEAST TO THE ONES
INCREASED RISK TO DEVELOP
ALZHEIMER'S.
AND THE LAST THING I WANTED TO
MENTION, THE PROJECT THAT WE HAD
CALLED EXTREME FOR THE LACK OF A
BETTER GAME I CALLED IT EXTREME
FOR THIS I WANTED TO GO TO
EXTREME TO GO AFTER THE ONES
THAT ACTUALLY REMAIN AND
IMPAIRED AS PART OF THE KINDRED
TO SEE IF WE CAN FIND CLOSE FOR
PROTECTION AGAINST COGNITIVE
DECLINE AND DEMENTIA AND THIS
WAS LAUNCHED IN 2017 AND AS A
REMINDER IN INDIVIDUALS FROM
THIS KINDRED THEY USUALLY
DEVELOP IMPAIRMENT AROUND THE
AGE OF 44 AND DEMENTIA AROUND
THE AGE OF 49 SO WE WERE AFTER
TTHE ONEST ARE OLDER THAN 60
OR 65.
THE FIRST CASE IS THE ONE THAT
WE REPORTED IN 2019 AND SHE WAS
72 WHEN SHE STARTED SHOWING
SIGNS OF COGNITIVE DECLINE.
ALMOST THREE DECADES AFTER THE
EXPECTED AGE OF CLINICAL ONSET
AND THE FAMILY BROUGHT HER TO
THE DOCTOR IN COLOMBIA AND BY
THE TIME SHE WAS SEEN BY HIM SO
SHE WAS RELATIVE LOW HEALTHY AND
THE ONLY THING THAT WAS HER
MEDICAL HISTORY SHE HAD HIGH
LEVELS OF CHOLESTEROL.
NOTHING THAT WAS QUITE
SIGNIFICANT.
SO SHE WASN'T BROUGHT IN COLBOS
AND SHE CAME TO IMAGING AND I'M
GOING TO WALK YOU THROUGH THE
IMAGING FINDINGS HERE.
YOU ARE NOT SEEING WHAT I'M
SEEING.
OK.
SO, HERE YOU CAN SEE THE AMYLOID
PATHOLOGY AND ALL THIS TIME I
WAS JUST CLICKING HERE.
I APOLOGIZE.
SO THE AMYLOID HERE THIS IS
COMPARED TO THE TYPICAL MCI AND
YOU CAN SEE THE LAYERS OF
AMYLOID WERE REALLY HIGH, THE
HIGHEST WE'VE SEEN IN ANYBODY IN
THE KINDRED AND THE SECOND ROW
HERE IS THE LAYERS OF TAU SO
THIS IS COMPARED TO THE MCI AND
YOU CAN SEE THE LEVELS OF TAU
WERE VERY LIMIT AND JUST VERY
LIMITED IN DEALS SO IN THE
LOCATION AND THE TAU WAS
ACTUALLY ACCUMULATING AND THE
WAY TO SEE IT IT HERE AND SO
SHE'S THE ONE IN RED AND
EVERYTHING ELSE WE HAVE AT THAT
POINT IN THE KINDRED, THE
BLACK -- THE BLACK ONE IS THE M.
>> CatherineCIAND THE CARRIERS E
AMYLOID HERE AND YOU HAVE TAU
HERE SO THE RED.
HIGH LEVELS OF AMYLOID AND
LIMITED LEVELS OF TAU AND WE RUN
SOME STRUCTURAL IMAGING AND THE
SAME SHE'S THE ONE IN RED SO HER
LEVELS OF ATROPHY WERE LIMITED
AND WHEN WE SEE HER FIRST AND
SHE HAD NO LAYERS OF METABOLISM
WHEN WE SAW HER AND IT'S WHAT WE
SAW THERE AND ALSO WHAT YOU SEE
IN THIS PICTURE RIGHT HERE.
SO YES, THE IMAGING SHOWED US
YOU HAVE A LIMITED TAU PATHOLOGY
AND DESPITE HAVING REALLY HIGH
LEVELS OF AMYLOID AND THE OTHER
THING THAT WE DID IS THAT WE
TOOK OUT A REALLY CLOSE LOOK NO
THE TAU LEVELS AND THIS IS LIKE
A FLOOD MAP FOR HER TEMPORAL
LOBE CORTEX AND IT DOES THE
CORTEX AND CAN YOU SEE THAT SHE
HAS A LITTLE TAU IN THE CORTEX
BUT NOTHING COMPARED WHEN YOU
ACTUALLY LOCK AT THE C AND THE D
AND IT'S SOMEONE THAT IS A
SYMPTOMATIC FROM THE KINDRED
THERE'S A TED AND YOU COMPARE
HER WITH A CONTROLLER IT'S THE
SAME CHROME WE HAVE IN THE
PREVIOUS SLIDE AND IT WAS A
44--YEAR-OLD CARRIERS.
SO PRETTY MUCH HAD LAYERS OF TAU
WHERE EXTREMELY LIMITED COMPARED
TO ANYONE IN THE INTRIED SO WE
RAN SOME GENETIC ANALYSIS ON HER
AND FIRST WE CONFIRMED SHE WAS A
CARRIER AND THE MUTATION AND WE
ALSO FOUND THAT SHE WAS ALMOST
HIGH FOR THE RIGHT MUTATION
WHICH IS AND SO WE MUTATIONS AND
WE START WITH THIS AND WE LOOKED
ANOTHER THE LOCATIONS
LIMITATIONS AND AROUND THE AMINO
ACID 136 AND CRITICAL FOR TWO
FUNCTIONS, BINDS TO THE LDL
RECEPTOR AND THE GLYCO SAM INK
OWE GLYCANS SO PREVIOUS WORK BY
OTHERS AND HAS SHOWN AND YOU
PROBABLY HAVE FAMILIAR WITH THIS
AS WELL THAT THE LDL RECEPTORS
HAS A HIGH AFFINITY WITH 8.4
FOLLOWED BY 8.3 AND FOLLOWED BY
SOMETHING RATE NOW AND IT HAS
AFFINITY ABOUT 30% AND BIND TO
GO THESE LDL BUT IT'S SOMETHING
THAT I WAS KNOWN BY THEN AND IT
WAS LIKE THE CHRISTCHURCH FOR
INSTANCE IN THIS BINDING WITH
HSPG AND THERE WAS SOMETHING
THAT BASED ON THE LOCATION, AS I
MENTIONED IT WAS LIKE PREDICTED
BUT IT WAS NOT AT THE TIME AND
AT LEAST IT WAS NOT REPORTED IN
THE LEADERSHIP AND IT WAS CLEAR
AND RELEVANT AT THAT POINT AND
GOING AFTER HSPG WAS IMPORTANT
BECAUSE YOU CAN SEE HERE, HSPG
IS IMPLICATED IN STEPS OF THE
PATHOLOGY OF ALZHEIMER'S DISEASE
INCLUDING THE REGULATION OF THIS
ACTIVITY AND REGULATION AMYLOID
AND INFLAMMATION AND TAU OUT
TAKE AND IT WAS INTERESTING FOR
US TO SEE THAT MAYBE FOR SOME
KIND OF IT WAS 30 YEARS FOR
SOMEONE IN THE KINDRED MAYBE FOR
SOMETHING LIKE THAT, THE
MECHANISMS AND THE PROTECTION
NODED TO BE SOMETHING THAT
CROSSED THE PATHOLOGY OR TIME OF
DISEASE AT DIFFERENT LEVELS ALL
THE WAY FROM AMYLOID TO PATH OLE
GOUGH AND IT MIGHT BE SOMETHING
LIKE BASE COULD PROVIDE THAT
ANSWER AND I PASS IT TO MY
COLLEAGUES, THE BASIC
SCIENTISTS, AND SOME OF THE
EXPERIMENTS THAT WERE CONDUCTED
HERE AND IT WAS ACTUALLY
CONDUCTED AT A LAB IN POSTDOCS
AND ONE OF THE FIRST EXMENTS TO
START UNDER THE MOLECULAR
CONSEQUENCES OF A CHRISTCHURCH
AND THE FIRST ONE THEY MEASURED
INVOTE ROW AND THEY ACTUALLY
FOUND THAT CHRISTCHURCH WAS A
COMPARED TO THE 8.3 AND HAD
LOWER AGGREGATION AND IN THE
SECOND SET OF THE EXPERIMENTS
THEY USED A JUST TO START
UNDERSTANDING THIS INTERACTIONS
BETWEEN CHRISTCHURCH AND HSPG
AND THEY FOUND THAT THE
INTERACTION OF THE 8.4 WAS
STRONG AND IT WAS LESS STRONG
WITH THE POINT HERE.
IT WAS STONG WITH 8.2 AND WHAT
WAS REMARKABLE WAS THE
ASSOCIATION WITH 8.3 CHRIST HER
WAS MUCH WEAKER COMPARED TO THE
OTHER AND IT'S SOMETHING YOU CAN
SEE HERE.
QUITE REMARKABLE, THE WEAKEST
STRAINS OF THE ASSOCIATION THAT
WAS OBSERVED WAS IN ONE WITH A
CHRISTCHURCH.
AND THEN, AS A PROOF OF
PRINCIPLE WE DESIGNED AND TEST
WHETHER THESE MECHANISMS COULD
BE TRANSLATED IN THE FUTURE AND
IT WOULD DESIGN AN ANTI BODY TO
MIMIC THE ROLE OF THE
CHRISTCHURCH AROUND THIS
LOCATION AND AS WE 136 AND THIS
IS PRESENTED HERE.
PRETTY MUCH YOU CAN SEE, YOU CAN
ACTUALLY SEE WHEN YOU USE THE
ANTIBODY THAT RECOGNIZED THE
APOE THE ANTIBODY THAT RECOGNIZE
APOE3 MIMICS THE INHIBITING THE
BINDING TO PRETTY MUCH ALL
TOGETHER, THE CONCLUSION OF
THESE THREE EXPERIMENTS,
CHRISTCHURCH IN VITRO REGULATES
AND MODULATES DEROGATION OR
AMYLOID WHICH IS INTRIGUING
ITSELF AND THEY HAVE A LOT OF
AMYLOID ON HER BRAIN SO IT COULD
HAVE BEEN WORSE IS THERE WAS NO
CHRISTCHURCH THERE AND WE FOUND
THEY IMPAIR THIS BINDING AND
ALSO WE SHOW AN ANTI BODY THAT
RECOGNIZES APOE3 AROUND THIS
REGION OF AMINO ACID 136 WHERE
CHRIST CHRISTCHURCH COULD SUGGEA
POTENTIAL THERAPEUTIC AND BASED
ON THESE FINDINGS, MY
COLLABORATORS AND MY OTHERS ARE
PURSUING POTENTIAL THERAPEUTIC
SO THE MAIN CONCLUSION OF THIS
CASE IS LIKE THE SAME THAT THE
IMPACT OR APOE IS NOT LIMITED TO
AMYLOID AGGREGATION AND IT'S
ALSO SOMETHING THAT MAY IMPACT
OUR DIRECTLY OR INDIRECTLY THE
EFFECT TAU PROPAGATION AND WE
LEARNED THAT THIS PROTECTION
ESPECIALLY IN LID WHY'S CASE MAY
BE AT LEAST IN PART BY THE
MAGNITUDE OF THESE BINDINGS
BETWEEN APOE-HSPG AND WE LEARNED
THAT MAYBE ANTIBODIES, SOMETHING
THAT IS A SMALL MOLECULE MAY
INTERFERE BETWEEN APOE AND HSPG
CAN REDUCE THE FUNCTIONS MAY
ACTUALLY HAVE A MAJOR IMPACT SO
WE HAVE BEEN WORKING ON THESE
FOR THE PAST FEW YEARS AND
HOPEFULLY THE FUTURE I CAN SHARE
MORE ABOUT THESE UPDATES BUT
LIKE WORKING OF COURSE IN
UNDERSTANDING THE MECHANISMS ON
THESE NEURO PROTECTION AND
RUNNING MODERN INVETO AND
MODELS, WE ARE ALSO WORK AND I'M
GOING TO BRIEFLY MENTION THE
WORK WORE DOING UNDERSTANDING
THE IMPACT OR CHRISTCHURCH IN
PSYGOATS WHEN WE ONLY HAVE ONE
COPY AND AS I MENTIONED BEFORE,
SO, DONNA LYDIA IS ONLY THE
FIRST ONE IN THE PROTECT WE WERE
ABLE TO IDENTIFY OTHER OUTLIERS
AND WE ARE IN THE PROCESS OF
CHARACTERIZING THE OTHER ONES AS
WELL.
SO AS A QUICK UPDATE, SO, WITH
Dr. LOPITA IF APOE
CHRISTCHURCH CAN BE PROTECTIVE
IN COLLABORATION WITH DOCTORS,
WE ACTUALLY CHARACTERIZE APOE IN
2,000 FROM THE CARRIERS FROM THE
COLUMBIAN CARRIERS INCLUDING THE
CHRISTCHURCH MUTATION AND WE
ACTUALLY IDENTIFIED 97 OF THE
MEMBERS THAT HAVE THE
CHRISTCHURCH MUTATION INCLUDING
84 WHO ARE LIVING AND 13 WHO ARE
DECEASED BUT OUT OF THOSE 13
SEVEN WERE BRYN DONORS AND OUT
OF THESE 84, 29 OF THEM ACTUAL
LOW HAVE BOTH MUTATIONS AND THE
APOE3 AND THE E280A VARIATION SO
WE'RE FALLING THIS 84 AND
CHARACTER EYES THIS IN THE PAST
YEAR SO IN THE PAST YEAR, ALL
THE 84 WERE RECONTACTED AND THEY
STARTED UNDERGOING COMPREHENSIVE
CLINICAL ASSESSMENTS, MIs AND
PRETTY MUCH ALL THE IMAGING THAT
CAN BE DONE IN COLOMBIA AND
SO -- SORRY.
DID I DO SOMETHING WRONG?
THE AGE RANGE FOR THE CARRIERS
GOES FROM 17 TO 72 YEARS AND
ENCLOUDS 11 THAT HAVE THE TWO
MUTATIONS THAT ACTUALLY ARE FROM
50 TO 72 AND FROM THOSE I PRETTY
MUCH AS I MENTIO MENTION BEF 50Y
OLDER AND WE ONLY CHARACTERIZE
FOR AIC SO WE'RE SAYING THIS SO
FOR CHARACTERIZING THE FIRST
THROW, THE COGNITIVE PERFORMANCE
THAT WE REVIEW FOR THIS
INDIVIDUALS THEY ACTUALLY FELL
WITHIN THE NORMAL RANGE COMPARED
TO THE AGE MASS IN INDIVIDUALS
FROM TH THE KINDRED AND THE MRID
HOPEFULLY BY THE TIME THAT WE
PRESENTED IT, WE WILL HAVE DATA
ON THOSE INDIVIDUALS AS WELL.
SO WE HAVE ONE INDIVIDUAL THAT
ACTUAL LOW HAD A TRAVEL TO
BOSTON FOR TAU IMAGES AND GOING
BACK TO THE CORTEX THIS IS HOW
THEY TAU IMAGING LOCKS FOR
SOMEONE WITH ONLY ONE COPY AND
SO THE SAYING LIKE IT COMPARED
TO ANYBODY IN THE KINDRED, EVEN
AFTER TWO YEARS OF FOLLOW-UP SO
THIS IS PRELIMINARY BUT FIRST
THE PREVALENCE RATE OF
CHRISTCHURCH AND IT'S VERY HIGH
COMPARED TO THE GENERAL
POPULATION AND IT'S SOMETHING
THAT THE FIRST BIG NEWS THERE
AND THE PRELIMINARY DATA THAT WE
HAVE IS VERY PRELIMINARY BUT
TALKS THEY MAY HAVE SOME LEVEL
OF PROTECTION WITHIN THE TWO
STUDY AND WE NEED TO CONTINUE
WITH THE CHARACTERIZATION BUT
THE IDEA IS TO SEE IF
CHRISTCHURCH CAN ONLY PROTECTED
FOR THE ONES IN BRAZIL AND ONE
MUTATION SO AWFUL THESE ARE THE
SAME TO HOW MUCH WE CAN ACTUALLY
LEARN FROM ONE PATIENT AND THIS
IS GOING BACK TO THE CLINIC,
IT'S IMPORTANT TO TAKE IT FROM
THE CLINIC AND HOW MUCH ONE
PATIENT CAN TEACH US ABOUT
GENOMICS AND BASIC SIGNS AND
HOPEFULLY IN THE FUTURE OR SO
THEY TEACH US DRUG DISCOVERY AND
CLINICAL TRIALS AND TO CONCLUDE,
SO HOPEFULLY I CONVINCE YOU THAT
THEY WORK WITH THE FAMILIES AND
MUTATIONS AND PROVIDE A UNIQUE
OPPORTUNITY TO CLINICAL TO
CLINICAL STAGES AND TO DEVELOP
INFORMATIONS FOR EARLY DOUGH
TEXT TO AVAILABLE INTERVENTIONS
AND CLINICAL TRIALS AND DEVELOP
FOR CHARACTERIZE THE BIOMARKER
TRAJECTORY AND THERE'S MORE TO
LEARN FROM THIS AND MUTATIONS
AND THOSE INDIVIDUALS THAT ARE
UNIMPAIRED AND SO WE SHOULD
ENCLOUD MORE FAMILIAR LESS IN LE
FUTURE.
THIS TAKES A VILLAGE AND I WOULD
LIKE TO ACKNOWLEDGE EVERYBODY
THAT'S BEEN PART OF THE CALL OF
THIS STUDY.
EVERYBODY IN MY LAB, MY MENTORS,
AND THE DOCTORS AND
THE FAMILIES IN COLOMBIA FOR
THEIR DEDICATION TO RESEARCH AND
MY FUNDING IN SUPPORT AS WELL.
THANK YOU, VERY MUCH.
[APPLAUSE]
>> WOULD YOU LIKE TO START WITH
A QUESTION?
I HAVE A FEW MORE.
FIRST, LET ME REPEAT THAT THE
CNE CODE AND THAT IS 37950.
I'LL ASK ONE QUESTION.
I'LL TRY TO READ THIS LOWLY.
HEPERIN SULPHATE PROTO GAELYNN
ARE FOR MODE ABLE HUMAN VIRUSES.
WHEN YOU LOOKED FOR SIGNS OF
VIRUS INFECTION AS A POSSIBLE
RISK OR PROTECTION FACTOR?
>> THAT'S A GOOD POINT.
NO WE HAVEN'T BUT WE SHOULD,
YEAH.
>> THANK YOU.
>> YEAH.
>> COUPLE OF QUESTIONS.
FIRST, AMONG THE MANY STRIKING
FINDINGS, ONE WAS MENTIONED IF I
HEARD CORRECTLY IS THAT CARRIERS
HAD AN INCREASE IN SINGULAR
CORTEX GRAY MATTER.
DO YOU HAVE ANY IDEA WHAT MAKES
UP THAT INCREASED MASS?
NO.
ONE OF THE ISSUES WE DISCUSSED
IN THE PAPER AND THIS IS LIKE
GOING BACK TO THE COMMUNITY
REFERS TO THE FINDINGS IN THE
LIFESPAN AND THE CHILDREN.
ONE OF THE THINGS WE DISCUSSED
IT COULD BE RELATED WITH
INFLAMMATION.
>> IT'S EARLY SO YOU DON'T HAVE
POSTMORTEM EXAMINATION YET.
>> EXACTLY.
>> ANOTHER VERY DIFFERENT
QUESTION, IN THE I DO DIANNE
STUDY, THEY LOOKED AT MUCH
SMALLER INDIVIDUAL FAMILIES AND
MULTIPLE OTHER OF THEM A CROSS
THE WORLD.
I JUST KNOW THE BEHAVIOR OF THE
SOCIOLOGY OF THAT FAMILY OFTEN
THEY DO WANT TO KNOW THEIR
TYPING AND IT LEADS TO
INTERESTING STRATEGIES FOR
CLINICAL STUDIES AND TRIALS.
CAN YOU COMMENT ON WAS THERE A
PHENOMENON IN THE COLOMBIA
COHORT?
>> THEY DON'T WANT TO KNOW THE
STATUS.
>> THIS IS VERY GOOD QUESTION.
RIGHT NOW FOR INSTANCE, WE ARE
GOING TO PRESENT SOME OF THE
RESORTS OF THE PILOT STUDY
CONDUCTED ABOUT THAT SO WE
PRETTY MUCH I DON'T WANT TO TELL
YOU EVERYTHING THAT'S GOING TO
BE THERE BUT NUCLEAR FAMILY BY
NUCLEAR FAMILY SO THERE ARE SOME
FAMILIES THAT THEY ARE MORE
INCLINED TO KNOW AND SOME OTHER
FAMILIES THEY REALLY DON'T WANT
TO KNOW.
SO YEAH.
IT VARIES.
>> THIS IS FROM ONE OF OUR
RESEARCHERS HERE.
VERY BEAUTIFUL RESULTS.
EXALT OF THE DATA AND TESTING
PRESENTED RELATED DIRECTLY TO
AMYLOID AND TAU.
WHAT IS THE DATA AVAILABLE
RELATED TO THE INFLAMMATORY
ASPECTS OF THE DISEASE IN THIS
KINDRED.
BLOOD OR PET BIOMARKERS THAT
WERE DONE?
THIS MAY BE ESPECIALLY IMPORTANT
IN THE APOE CARRIERS AS WELL.
>> THAT'S AN EXCELLENT QUESTION.
THE ANSWER IS LIKE WE ACTUALLY
HAVE MARKERS OF THE NEW
INFLAMMATION YET BUT AS I
MENTIONED IN ONE OF THE SLIDES,
IT'S SOMETHING THAT IS ON GOING
SO NOW WE'RE COLLECTING
ESPECIALLY CSF AND WE ARE GOING
TO START MEASURING MARKERS ON
INFLAMMATION IN CSF IN THE
FUTURE WE ARE HARD TO MEASURE IN
PLASMA BUT MARKERS ON THE
INFLAMMATION IS TO MEASURE IN
CSF SO WE'RE COLLECTING IT AND
WE'LL HAVE AN ANSWER FOR THAT
BUT WE HAVEN'T DONE IT YET.
>>THANK YOU VERY MUCH, THAT WAS
BEAUTIFUL PRESENTATION.
IN REGARD TO THE PET IMAGES ON
THE COLOMBIA KINDRED, CAN YOU
TELL IF THEY HAD A SIMILAR
HETERO AGAIN EIGHT TEE WHAT IS
DESCRIBED IN SPORADIC SOME THAT
ARE MORE LIKE POSTER YEAR AND
OTHER ANTERIOR AND OTHER HIM PA
CAM PA SPARING OR DO THEY LOCK
AT TAU IMAGING VERY SIMILAR,
PRETTY HOMOGENEOUS?
>> SO, I CAN GIVE YOU LIKE TWO
ANSWERS.
SO THE FIRST ONE IS LIKE, SO,
THE SAMPLE THAT WE HAVE IS VERY
SMALL AND IT'S VERY HOMOGENEOUS
SO PRETTY MUCH LIKE FOR
INSTANCE, SOMETHING THAT WE HAVE
SEEN IS WE STARTED LIKE FOR
INSTANCE MEASURING TAU IN OTHER
MUTATIONS AND THE SAME WAY WE
STARTED LOOKING AT OTHER
MUTATIONS AND THE PARTING OF TAU
ACCUMULATION AND IT'S TENDS TO
BE A VERY HOME YO GENIOUS SO
WHEN YOU LOOK AT THE PAIRING
THAT WE HAVE IT'S VERY -- THE
PAIRING AND ACCUMULATION OR TAU
IS VERY TYPICAL OR WHAT IS
CALLED LIKE A YOU SEE IT AS
ALZHEIMER'S DISEASE AND AS SOON
AS YOU STUDY TO USE OTHER
MUTATIONS YOU START SEEING THE
HETERO GAIN TEE.
>> THIS ONE IS INTERESTING SO I
WAS WONDERING THE SAME.
I SEEN STUDIES BACK AND FOURTH
SAYING COFFEE CONSUMPTION RAISES
THE RISK OF ALZHEIMER'S OR
REDUCES THE RISK.
THIS IS GREAT.
THIS DATA FROM COLOMBIA HAVE YOU
EXAMINED COFFEE CONSUMPTION IN
ALZHEIMER'S?
>> SO WE HAVEN'T.
SO YEAH, WE HAVEN'T AND WE
HAVEN'T ACTUALLY -- WELL, LET ME
SEE.
>> I DON'T KNOW IF THAT'S AN
ASSUMPTION THAT COFFEE
CONSUMPTION IS HIGHER IN
COLOMBIA.
IT'S WHERE IT COMES FROM?
>> EVERYBODY DRINKS COFFEE SO AT
END OF THE DAY WE WOULD HAVE IT.
SO WE ACTUAL WILL HE MENTIONED
LIKE, EATING HABITS, FOR
INSTANCE OR WE PROBABLY CAN'T
TAKE A LOOK AND SEE IF THERE'S
ANY DIFFERENT PARTICULAR LOW IS
HOW MANY THEY DRINK COFFEE AND
STUFF LIKE THAT SO WE'RE ALSO
MEASURING LIKE LIFESTYLE AND
STUFF LIKE THAT AND WE HAVE A
QUESTIONNAIRE ASKING FOR EATING
HABITS SO WE ASK WHAT THEY HAVE
AND WHAT THEY DRINK.
WE COULD LOOK AT THAT,
SPECIFICALLY BUT YEAH, WE
HAVEN'T ANALYZED THAT DATA YET.
EVERYBODY ACTUAL LOW HAS A
COFFEE IN THE MORNING SO IT'S
KIND OF LIKE, EVEN CARRIERS AND
NON CARRIERS.
WE CAN ACTUALLY LOOK AT THE
DATA.
>> ONE MORE QUICK ONE FROM --
THANK YOU FOR THE FASCINATING
TALK.
PERHAPS I MISSED THIS, HOW LONG
HAS THE COLOMBIA CAN KINDRED
BEEN KNOWN AND THIS IS BASED IN
INDIGENOUS POPULATIONS OR
EUROPEAN/SPANISH POPULATIONS?
>> SO THE MUTATION IN COLOMBIA
WAS DISCOVERED IN THE LATE
'80s.
SO THE ORIGINAL MUTATION WAS
ACTUALLY TRACKED BACK TO CON
KEYS DA DOR FROM SPAIN.
SO U.S. TRACKED TO SPAIN.
>> I WAS GOING TO ASK A MORE
GENERAL FORM OF THE QUESTION
ABOUT COFFEE AND YOU ANSWERED IT
ALREADY.
IN ADDITION TO LOOKING AT
GENETIC RISK OF PROTECTIVE
FACTORS, IN THIS POPULATION WITH
A SING MANY HOMO GENIOUS
MUTATION, A PLACE TO LOOK FOR
OTHER NON GENETIC FACTORS AND
YOU ALREADY ANSWERED SO YOU LOCK
AT VARIOUS ENVIRONMENTAL
EXPOSURES THAT MIGHT BE
PROTECTIVE OR AGGRAVATED OR
ACCELERATED.
>> WE COLLECTED ALL THE DATA,
YEAH.
THEY'RE LOOKING INTO THAT AND
SEE ABOUT THAT.
>> HAS THE COLOMBIA YAN COHORT
STUDIES BRAINS.
>> YEAH.
>> ANY INTERESTING REVELATION
THERE'S?
>> YOU MEAN FOR THE CASE OF THE
CHRISTCHURCH?
>> YEAH.
THAT WOULD BE GREAT, YEAH.
>> FOR THE CASE OF THE
CHRISTCHURCH WE ARE CURRENTLY
WORKING ON THE POSTMORTEM AND I
DIDN'T MENTION IT BUT
UNFORTUNATELY THE PATIENT DIED
EARLY OVER A YEAR AGO AND THE
FAMILY ACTUALLY DONATED THE
BRAIN FOR ANALYSIS AND WE ARE
CURRENTLY WORKING ON THE AN AM
SIS AND THE SAME LIKE IN COLBOS
THEY'RE PRE CLINICAL AND THEY'RE
STILL VERY YOUNG BUT THE SAME IS
PART OF THE WORK WE DO WITH THE
FAMILIES WE ALWAYS TALK AND
BRING DONATION AND IN COLOMBIA
THEY ACTUALLY HAVE A NEURO BANK
AND BRAIN BANK THAT HAS OVER 300
BRAINS FROM THE MUTATIONS.
SO, YES, WE LIKE TO LOOK INTO
THAT AND EVERY TIME WE TALK
ABOUT THE IMPORTANCE OR DONATING
THE BRAINS.
>> TERRIFIC.
>> ONE OTHER QUESTION JUST FOR
MY OWN KNOWLEDGE, YOU HAD TO
FIGURE WHERE YOU WERE LOCKING,
DIFFERENT PROFILES FOR AMYLOID
PATH OLE GOUGH AND THEN TAU
LEVELS OF TAU, AND YOU SAW THISP
SPIKE IN TAU AT 30 YEARS.
WHAT'S YOUR HYPOTHESIS OF WHAT
IS GOING ON IN THIS AGE-RELATED
MILESTONE THAT'S CAUSING THAT
SHARP INCREASE IN TAU?
>> SO, THE ANSWER IS I DON'T
KNOW.
I THINK THAT DEFINITELY THERE'S
SOMETHING THERE THAT WE ARE
TRYING IDENTIFY WHAT IT IS AND
WHAT IS ON THE HYPOTHESIS LIKE
INFLAMMATION AND THAT IS THERE
IN BETWEEN AND SOMETHING ELSE
THAT I NEEDED TO MENTION BECAUSE
IT'S SOMETHING ELSE THAT WE'RE
EXPLORING IT COULD BE LIKE WHITE
MATTER FOR INSTANCE, THAT IS
SOMETHING THAT WE ARE CURRENTLY
EXAMINING AS WELL AND YEAH,
PROBABLY THERE'S ANOTHER FACT OR
THERE THAT IS ALSO CONTRIBUTING.
>> THANK YOU.
>> ANY CONCLUDING REMARKS?
>> I WANTED TO THANK YOU SO MUCH
FOR FASCINATING TALK AND GREAT
ORIGINAL WORK AND MAYBE EXEMPLAR
THAT ONE CAN FIND A PLACE AND
NOVEL RESEARCH AREAS AND REAL
FIFTH EXCELERATE PROGRESS THE
WAY YOU HAVE AND IT'S BEEN AN
OUTSTANDING STORY AND A
PLAINTIFF FOR NIH TO PLAY A ROLE
IN SUPPORTING IT AND WE
APOLOGIES FOR THE INTENSITY OF
THE MEETINGS YOU HAD THIS
MORNING AND NOW YOU CAN REST AND
RELAX AND I THINK WE'VE GOT A
BAD ENOUGH TIME TO LET YOU SEE
THE FLORENCE MAHONEY MEMORIAL
GARDEN.
ON BEHALF OF ALL OF US, THANK
YOU FOR THE VISIT AND ALL THE
WORK THAT YOU DO.
>>THANK YOU, VERY MUCH.
EVERYBODY.