Michael C Donohue1, Setareh H Moghadam2, Allyson D Roe2, Chung-Kai Sun2, Steven D Edland3, Ronald G Thomas1, Ronald C Petersen4, Mary Sano5, Douglas Galasko2, Paul S Aisen2, Robert A Rissman6. 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.
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.
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