Plasma Aβ levels do not reflect brain Aβ levels

Cerebral accumulation of amyloid P protein (AP) is characteristic of Alzheimer disease (AD). AP can be detected in cerebrospinal fluid and in plasma. Although plasma Ap 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 A beta 40 and A beta 42 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 (lied a median of I year after blood collection. Plasma levels of A beta 40 and A beta 42 were not associated with any of the brain measures, even after adjusting for age and interval between plasma collection and death. The APOE epsilon 4 allele may modify the relationship between plasma A beta 42 and formic acid-extractable A beta 42, with an inverse correlation in APOE epsilon 4 carriers and a positive correlation in those lacking APOE '-4. We conclude that plasma levels of A beta 40 and A beta 42 are not robust correlates of histologic or biochemically assessed amyloid burdens in brain, although the influence of the APOE genotype should be further explored.