. Cerebrospinal fluid beta-amyloid 42 is reduced before the onset of sporadic dementia: a population-based study in 85-year-olds. Dement Geriatr Cogn Disord. 2003;15(3):169-76. PubMed.

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  1. The argument that A-beta alterations precede the onset of AD is reinforced by this interesting study of CSF A-beta levels in the oldest old. Decreased levels of A-beta 42 were found in nondemented oldest old subjects, and A-beta42 levels in the lower 50th percentile had an impressive odds ratio for predicting the development of dementia over the next 3 years. These findings are consistent with the notion that defective clearance, aggregation and or deposition of A-beta42 precede the onset of AD. Which of these factors is instrumental in sporadic AD, and what other risk factors play a role, remain open questions. The study did not find an increase in levels of either A-beta 40 or 42 before the onset of dementia, which provides some fuel for the argument against overproduction of A-beta being an initiating factor in sporadic AD. It is likely that studies of amyloid imaging will be carried out on people at risk for AD (by virtue of genetic mutations or age), and it will be interesting to see both imaging and CSF A-beta levels being utilized. It remains impractical to measure CSF A-beta levels as a screening test in older individuals. Plasma A-beta rises on average during aging, and we await more data from studies that are following up cognitively normal individuals whose plasma A-beta levels change over time or are in the highest part of the normal range.

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