Down

Syndrome and Demen-a

Ira T. Lo2, MD Child Neurologist Professor Emeritus University of California, Irvine

Prevalence of Demen-a in Down Syndrome

By age 40 years, all individuals with DS have the pathological changes of Alzheimer disease However, demen-a is not invariable even at older ages

Deni-on of demen-a
Demen-a is a general term that refers to a progressive loss of memory, judgment, language, complex motor skills, and other intellectual func-ons Alzheimer disease is the most frequent cause of demen-a

Plaques and tangles in DS

(Courtesy E. Head)

Deposi-on of brain amyloid in DS

Deposited rst in infancy and accumulates across the lifespan Early amyloid plaques are considered benign but there is already evidence of apoptosis or neuronal cell suicide.

Early Onset A in Down syndrome

Intact Neurons

4 months old an--A1-16 immunostaining in free-floating formic acid pretreated 50 m thick formalin-fixed sections.

Caspase products in benign plaques

Findings in a man with par-al trisomy 21

Has 2 not 3 copies of amyloid precursor protein gene Not demented at age 70 years Has very li2le amyloid binding in his brain compared to controls

Man with par-al trisomy 21

47XY +del (21)(q11.2q22.1)

Low amyloid binding in pa-ent with par-al trisomy 2009,2012

2.5

PIB SUVr by Region of Interest

SUVr (CB)

1.5

Temporal_Lobe Frontal_Lobe

Parietal_Lobe

0.5

0 pDS_2009 pDS_2012 DS_avg AD_avg MCI_avg NC_avg

There appears to be a compensatory response in the hippocampus before the age of demen-a onset- this provides a poten-al target for therapeu-c trials

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

Conclusions
Amyloid accumula-on in DS required for demen-a Treatment interven-ons that are successful at older ages may be targeted to younger age groups and improve cogni-ve func-oning Clinical trails for young adults with DS are underway

Collaborators and Support

Elizabeth Head-Univ Ky-neurobiology Richard Haier-imaging David Keator-imaging Gary Small and colleagues, UCLA-imaging Eric Doran-program manager Supported in part by HD25912, HD065160, AG16572 ; Alzheimer Associa-on; State of California, UCI MIND Ins-tute