Change in plasma Aß peptides and onset of dementia in adults with Down syndrome.
OBJECTIVE
To examine changes in levels of plasma amyloid-β (Aβ) peptides, Aβ42 and Aβ40, in relation to onset of Alzheimer disease (AD) in adults with Down syndrome (DS).


METHODS
Plasma Aβ42 and Aβ40 were measured at initial examination and at follow-up in a community-based cohort of 225 adults with DS who did not have dementia at baseline and were assessed for cognitive/functional abilities and health status and followed at 14- to 20-month intervals. We used Cox proportional hazards modeling to estimate the cumulative incidence of AD by Aβ peptide change group (increasing, no change, or decreasing), adjusting for covariates.


RESULTS
Sixty-one (27.1%) of the participants developed AD. At follow-up, a decrease in Aβ42 levels, a decrease in the Aβ42/Aβ40 ratio, and an increase in Aβ40 levels were related to conversion to AD. Compared with the group with increasing levels of Aβ42, the likelihood of developing AD was 5 times higher for those whose plasma Aβ42 levels decreased over follow-up (hazard ratio [HR] = 4.9, 95% confidence interval [CI] 2.1-11.4). Decreasing Aβ42/Aβ40 was also strongly related to AD risk (HR = 4.9, 95% CI 1.8-13.2), while decreasing Aβ40 was associated with lower risk (HR = 0.4, 95% CI 0.2-0.9).


CONCLUSIONS
Among adults with DS, decreasing levels of plasma Aβ42, a decline in the Aβ42/Aβ40 ratio, or increasing levels of Aβ40 may be sensitive indicators of conversion to AD, possibly reflecting compartmentalization of Aβ peptides in the brain.
Taub Institute for Research on AD and the Aging Brain, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA. ns24@columbia.edu
N
N
Schupf
W B
WB
Zigman
M-X
MX
Tang
D
D
Pang
R
R
Mayeux
P
P
Mehta
W
W
Silverman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications*; D016229:Amyloid beta-Peptides / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics; D015331:Cohort Studies; D004314:Down Syndrome / Q000097:blood* / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011569:Psychiatric Status Rating Scales; D013997:Time Factors
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)