Plasma amyloid levels and the risk of ad in normal subjects in the cardiovascular health studysymbol

To examine the association between incident Alzheimer disease (AD), and plasma Aβ1-40 and Aβ1-42 levels in normal and mild cognitive impairment (MCI) subjects in a subgroup of participants of the Cardiovascular Health Study Cognition Study. We determined the plasma Aβ1-40 and Aβ1-42 levels of 274 nondemented subjects (232 normals and 42 with MCI) in 1998-1999 and repeated the measurements in 2002-2003. The mean age of the subjects at baseline was 79.3 ± 3.6 years. We examined the association between Aβ levels and incident AD over the ensuing 4.5 years, controlling for age, cystatin C level (marker of glomerular function), apolipoprotein E-4 allele, Modified-Mini-Mental State Examination scores, and MRI-identified infarcts. In an unadjusted prospective model in normal subjects, both Aβ1-40 and Aβ1-42 levels in 1998-1999 were associated with incident AD (n = 55) in 2002-2003 (longitudinal analysis). In the fully adjusted multivariate model, neither Aβ1-42 nor Aβ1-40 nor their ratio was associated with incident AD. However, adjustment had a very small effect on point estimates for Aβ1-42, from an odds ratio (OR) of 1.61 (p = 0.007) in the unadjusted model to an OR of 1.46 (p = 0.08) in the fully adjusted model. In 2002-2003 (cross-sectional analysis), only the unadjusted models showed that both peptides were associated with AD. Plasma Aβ levels are affected by age and by systemic and CNS vascular risk factors. After controlling for these conditions, Aβ-40 and Aβ1-42 are weak predictors of conversion to Alzheimer disease (AD) in normal subjects and are only weakly associated with AD in cross-sectional analysis. Consequently, plasma levels of Aβ do not seem to be useful biomarkers for AD.