Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI

Previous studies of A beta plasma as a biomarker for Alzheimer's disease (AD) obtained conflicting results. We here included 715 subjects with baseline A beta(1-40) and A beta(1-42) plasma measurement (50% with 4 serial annual measurements): 205 cognitively normal controls (CN), 348 patients mild cognitive impairment (MCI) and 162 with AD. We assessed the factors that modified their concentrations and correlated these values with PIB PET, MRI and tau and A beta(1-42) measures in cerebrospinal fluid (CSF). Association between A beta and diagnosis (baseline and prospective) was assessed. A number of health conditions were associated with altered concentrations of plasma A beta. The effect of age differed according to AD stage. Plasma A beta(1-42) showed mild correlation with other biomarkers of A beta pathology and were associated with infarctions in MRI. Longitudinal measurements of A beta(1-40) and A beta(1-42) plasma levels showed modest value as a prognostic factor for clinical progression. Our longitudinal study of complementary measures of A beta pathology (PIB, CSF and plasma A beta) and other biomarkers in a cohort with an extensive neuropsychological battery is significant because it shows that plasma A beta measurements have limited value for disease classification and modest value as prognostic factors over the 3-year follow-up. However, with longer follow-up, within subject plasma A beta measurements could be used as a simple and minimally invasive screen to identify those at increased risk for AD. Our study emphasizes the need for a better understanding of the biology and dynamics of plasma A beta as well as the need for longer term studies to determine the clinical utility of measuring plasma A beta.