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Abstract
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.
Footnotes
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Study funding: Supported by the NIH (AG014763, HD35897, HD37425, and AG07232) and by New York State through its Office of Mental Retardation and Developmental Disabilities.
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- Aβ
- amyloid-β
- AD
- Alzheimer disease
- APP
- amyloid precursor protein
- CI
- confidence interval
- DS
- Down syndrome
- HR
- hazard ratio
- MCI
- mild cognitive impairment
- Received March 31, 2010.
- Accepted July 7, 2010.
- Copyright © 2010 by AAN Enterprises, Inc.
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