Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials

Abstract

Introduction: Little is known about the utility of plasma amyloid beta (Aβ) in clinical trials of Alzheimer's disease (AD).

Methods: We analyzed longitudinal plasma samples from two large multicenter clinical trials: (1) donezepil and vitamin E in mild cognitive impairment (n = 405, 24 months) and (2) simvastatin in mild to moderate AD (n = 225, 18 months).

Results: Baseline plasma Aβ was not related to cognitive or clinical progression. We observed a decrease in plasma Aβ40 and 42 among apolipoprotein E epsilon 4 (APOE ε4) carriers relative to noncarriers in the mild cognitive impairment trial. Patients treated with simvastatin showed a significant increase in Aβ compared with placebo. We found significant storage time effects and considerable plate-to-plate variation.

Discussion: We found no support for the utility of plasma Aβ as a prognostic factor or correlate of cognitive change. Analysis of stored specimens requires careful standardization and experimental design, but plasma Aβ may prove useful in pharmacodynamic studies of antiamyloid drugs.

Keywords: Alzheimer's disease; Apolipoprotein E; Bioassay; Biomarkers; Donepezil; Innogenetics; Luminex; Mild cognitive impairment; Plasma amyloid; Simvastatin.