ira lott: down syndrome and dementia

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DownSyndromeandDemen-a

IraT.Lo2,MD

ChildNeurologist

ProfessorEmeritus

UniversityofCalifornia,Irvine

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PrevalenceofDemen-ainDown

Syndrome

•  Byage40years,allindividualswithDShavethepathologicalchangesofAlzheimerdisease

•  However,demen-aisnotinvariableevenatolderages

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Defini-onofdemen-a

•  Demen-aisageneraltermthatreferstoa

progressivelossofmemory,judgment,

language,complexmotorskills,andother

intellectualfunc-ons

•  Alzheimerdiseaseisthemostfrequentcause

ofdemen-a

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PlaquesandtanglesinDS(CourtesyE.Head)

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Deposi-onofbrainamyloidinDS

•  Depositedfirstininfancyandaccumulates

acrossthelifespan

•  Earlyamyloidplaquesareconsidered

“benign”butthereisalreadyevidenceofapoptosisorneuronal“cellsuicide”.

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EarlyOnsetAβ in Down syndrome

4monthsold–an-Aβ1-16 immunostaining in free-floatingformic acid pretreated 50 µm thick formalin-fixed sections.

Intact

Neurons

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Caspaseproductsin“benign”plaques

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Findingsinamanwithpar-altrisomy

1

•  Hasnot3copiesofamyloidprecursor

proteingene

•  Notdementedatage70years

•  Hasveryli2leamyloidbindinginhisbrain

comparedtocontrols

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Manwithpar-altrisomy1

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47XY+del(1)(q11.q.1)

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0

0.5

1

1.5

.5

pDS_009 pDS_01 DS_avg AD_avg MCI_avg NC_avg

      S      U      V     r       (      C      B       )

PIBSUVrbyRegionofInterest

Temporal_Lobe

Frontal_Lobe

Parietal_Lobe

Lowamyloidbindinginpa-entwith

par-altrisomy009,01

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Thereappearstobea“compensatoryresponse”in

thehippocampusbeforetheageofdemen-aonset

thisprovidesapoten-altargetfortherapeu-ctrials

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FDG uptake in hippocampus, increased in young adults withDS, decreased in AD patients general population

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Conclusions

•  Amyloidaccumula-oninDSrequiredfordemen-a

•  Treatmentinterven-onsthataresuccessfulatolderagesmaybetargetedtoyoungerage

groupsandimprovecogni-vefunc-oning

•  ClinicaltrailsforyoungadultswithDSare

underway

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CollaboratorsandSupport

•  ElizabethHeadUnivKyneurobiology•  RichardHaierimaging

•  DavidKeatorimaging

•  GarySmallandcolleagues,UCLAimaging

•  EricDoranprogrammanager

•  SupportedinpartbyHD591,HD065160,AG1657;AlzheimerAssocia-on;Stateof

California,UCIMINDIns-tute