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Scientific article
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English

Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort

Published inJournal of Alzheimer's Disease, vol. 74, no. 1, p. 213-225
Publication date2020
Abstract

We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.

Keywords
  • Alzheimer's disease
  • Amyloid-β
  • Biomarkers
  • Plasma
  • Proteomics
Funding
  • Swiss National Science Foundation - 320030_141179
  • European Commission - European Medical Information Framework [115372]
Citation (ISO format)
WESTWOOD, Sarah et al. Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer’s disease multimodal biomarker discovery cohort. In: Journal of Alzheimer’s Disease, 2020, vol. 74, n° 1, p. 213–225. doi: 10.3233/JAD-190434
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Article (Published version)
Identifiers
ISSN of the journal1387-2877
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Technical informations

Creation07/10/2020 2:30:00 PM
First validation07/10/2020 2:30:00 PM
Update time03/15/2023 10:29:10 PM
Status update03/15/2023 10:29:06 PM
Last indexation02/12/2024 1:17:36 PM
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