Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials

Michael C. Donohue, Setareh H. Moghadam, Allyson D. Roe, Chung Kai Sun, Steven D. Edland, Ronald G. Thomas, Ronald Carl Petersen, Mary Sano, Douglas Galasko, Paul S. Aisen, Robert A. Rissman

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Article number1909
Pages (from-to)1069-1079
Number of pages11
JournalAlzheimer's and Dementia
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2015

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Keywords

  • Alzheimer's disease
  • Apolipoprotein E
  • Bioassay
  • Biomarkers
  • Donepezil
  • Innogenetics
  • Luminex
  • Mild cognitive impairment
  • Plasma amyloid
  • Simvastatin

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy

Cite this

Donohue, M. C., Moghadam, S. H., Roe, A. D., Sun, C. K., Edland, S. D., Thomas, R. G., Petersen, R. C., Sano, M., Galasko, D., Aisen, P. S., & Rissman, R. A. (2015). Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials. Alzheimer's and Dementia, 11(9), 1069-1079. [1909]. https://doi.org/10.1016/j.jalz.2014.07.156