title: Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Donohue
authors.affiliation: Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA.
authors.forename: Setareh H
authors.initials: SH
authors.lastname: Moghadam
authors.affiliation: Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA.
authors.forename: Allyson D
authors.initials: AD
authors.lastname: Roe
authors.affiliation: Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA.
authors.forename: Chung-Kai
authors.initials: CK
authors.lastname: Sun
authors.affiliation: Department of Family Preventive Medicine, University of California San Diego, School of Medicine, San Diego, CA, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Edland
authors.affiliation: 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.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.affiliation: 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.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: 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.
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.affiliation: Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.affiliation: Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California San Diego, School of Medicine, San Diego, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: 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.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rissman
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D060825:Cognitive Dysfunction / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D018450:Disease Progression; D000077265:Donepezil; D005260:Female; D006579:Heterozygote; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D018697:Nootropic Agents / Q000627:therapeutic use; D010446:Peptide Fragments / Q000097:blood*; D010880:Piperidines / Q000627:therapeutic use; D012720:Severity of Illness Index; D019821:Simvastatin / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D007189:Indans; D018697:Nootropic Agents; D010446:Peptide Fragments; D010880:Piperidines; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D014810:Vitamin E; D000077265:Donepezil; D019821:Simvastatin
keywords: Alzheimer's disease; Apolipoprotein E; Bioassay; Biomarkers; Donepezil; Innogenetics; Luminex; Mild cognitive impairment; Plasma amyloid; Simvastatin