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Alzheimers Dement. 2015 Sep;11(9):1069-79. doi: 10.1016/j.jalz.2014.07.156. Epub 2014 Oct 7.

Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials.

Author information

1
Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA; Department of Family Preventive Medicine, University of California San Diego, School of Medicine, San Diego, CA, USA.
2
Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA.
3
Department of Family Preventive Medicine, University of California San Diego, School of Medicine, San Diego, CA, USA.
4
Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA; Department of Neurology, Mayo Clinic Alzheimer's Disease Research Center, Department of Health Sciences Mayo Clinic College of Medicine, Research, Rochester, MN, USA.
5
Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA; Mount Sinai School of Medicine and James J. Peters Veterans Association Medical Center, Bronx, NY, USA.
6
Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA. Electronic address: rrissman@ucsd.edu.

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

PMID:
25301682
PMCID:
PMC4387108
DOI:
10.1016/j.jalz.2014.07.156
[Indexed for MEDLINE]
Free PMC Article

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