Plasma AA Levels Do Not Reflect Brain AA Levels

Cerebral accumulation of amyloid A protein (AA) is characteristic of Alzheimer disease (AD). AA can be detected in cerebrospinal fluid and in plasma. Although plasma AA 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 AA40 and AA42 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 AA40 and AA42 were not associated with any of the brain measures, even after adjusting for age and interval between plasma collection and death. The APOE ?4 allele may modify the relationship between plasma AA42 and formic acid-extractable AA42, with an inverse correlation in APOE ?4 carriers and a positive correlation in those lacking APOE ?4. We conclude that plasma levels of AA40 and AA42 are not robust correlates of histologic or biochemically assessed amyloid burdens in brain, although the influence of the APOE genotype should be