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 Citations (Scopus)

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

Fingerprint

Amyloid
Alzheimer Disease
Clinical Trials
Simvastatin
Apolipoprotein E4
Vitamin E
Multicenter Studies
Research Design
Placebos
Pharmaceutical Preparations

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., ... 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

Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials. / Donohue, Michael C.; Moghadam, Setareh H.; Roe, Allyson D.; Sun, Chung Kai; Edland, Steven D.; Thomas, Ronald G.; Petersen, Ronald Carl; Sano, Mary; Galasko, Douglas; Aisen, Paul S.; Rissman, Robert A.

In: Alzheimer's and Dementia, Vol. 11, No. 9, 1909, 01.09.2015, p. 1069-1079.

Research output: Contribution to journalArticle

Donohue, MC, Moghadam, SH, Roe, AD, Sun, CK, Edland, SD, Thomas, RG, Petersen, RC, Sano, M, Galasko, D, Aisen, PS & Rissman, RA 2015, 'Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials', Alzheimer's and Dementia, vol. 11, no. 9, 1909, pp. 1069-1079. https://doi.org/10.1016/j.jalz.2014.07.156
Donohue MC, Moghadam SH, Roe AD, Sun CK, Edland SD, Thomas RG et al. Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials. Alzheimer's and Dementia. 2015 Sep 1;11(9):1069-1079. 1909. https://doi.org/10.1016/j.jalz.2014.07.156
Donohue, Michael C. ; Moghadam, Setareh H. ; Roe, Allyson D. ; Sun, Chung Kai ; Edland, Steven D. ; Thomas, Ronald G. ; Petersen, Ronald Carl ; Sano, Mary ; Galasko, Douglas ; Aisen, Paul S. ; Rissman, Robert A. / Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials. In: Alzheimer's and Dementia. 2015 ; Vol. 11, No. 9. pp. 1069-1079.
@article{453b288581144ca896349fd5a10d9721,
title = "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",
author = "Donohue, {Michael C.} and Moghadam, {Setareh H.} and Roe, {Allyson D.} and Sun, {Chung Kai} and Edland, {Steven D.} and Thomas, {Ronald G.} and Petersen, {Ronald Carl} and Mary Sano and Douglas Galasko and Aisen, {Paul S.} and Rissman, {Robert A.}",
year = "2015",
month = "9",
day = "1",
doi = "10.1016/j.jalz.2014.07.156",
language = "English (US)",
volume = "11",
pages = "1069--1079",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials

AU - Donohue, Michael C.

AU - Moghadam, Setareh H.

AU - Roe, Allyson D.

AU - Sun, Chung Kai

AU - Edland, Steven D.

AU - Thomas, Ronald G.

AU - Petersen, Ronald Carl

AU - Sano, Mary

AU - Galasko, Douglas

AU - Aisen, Paul S.

AU - Rissman, Robert A.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Apolipoprotein E

KW - Bioassay

KW - Biomarkers

KW - Donepezil

KW - Innogenetics

KW - Luminex

KW - Mild cognitive impairment

KW - Plasma amyloid

KW - Simvastatin

UR - http://www.scopus.com/inward/record.url?scp=84942198358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942198358&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2014.07.156

DO - 10.1016/j.jalz.2014.07.156

M3 - Article

C2 - 25301682

AN - SCOPUS:84942198358

VL - 11

SP - 1069

EP - 1079

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 9

M1 - 1909

ER -