Plasma Aβ Levels Do Not Reflect Brain Aβ Levels

Abstract

Cerebral accumulation of amyloid beta protein (Abeta) is characteristic of Alzheimer disease (AD). Abeta can be detected in cerebrospinal fluid and in plasma. Although plasma Abeta has been proposed as a marker of risk of AD, it is unknown how plasma levels relate to neuropathologic levels. We compared plasma levels of Abeta40 and Abeta42 obtained during life with biochemical and pathologic levels in frontal and temporal neocortex in 25 individuals (17 AD, 3 control, and 5 non-AD dementia) who died a median of 1 year after blood collection. Plasma levels of Abeta40 and Abeta42 were not associated with any of the brain measures, even after adjusting for age and interval between plasma collection and death. The APOE epsilon4 allele may modify the relationship between plasma Abeta42 and formic acid-extractable Abeta42, with an inverse correlation in APOE epsilon4 carriers and a positive correlation in those lacking APOE epsilon4. We conclude that plasma levels of Abeta40 and Abeta42 are not robust correlates of histologic or biochemically assessed amyloid burdens in brain, although the influence of the APOE genotype should be further explored.