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Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort

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DOI

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  • Sarah Westwood
  • Alison L Baird
  • Sneha N Anand
  • Alejo J Nevado-Holgado
  • Andrey Kormilitzin
  • Liu Shi
  • Abdul Hye
  • Nicholas J Ashton
  • Angharad R Morgan
  • Isabelle Bos
  • Stephanie J B Vos
  • Susan Baker
  • Noel J Buckley
  • Mara Ten Kate
  • Philip Scheltens
  • Charlotte E Teunissen
  • Rik Vandenberghe
  • Silvy Gabel
  • Karen Meersmans
  • Sebastiaan Engelborghs
  • Ellen E De Roeck
  • Kristel Sleegers
  • Giovanni B Frisoni
  • Olivier Blin
  • Jill C Richardson
  • Régis Bordet
  • José L Molinuevo
  • Lorena Rami
  • Anders Wallin
  • Petronella Kettunen
  • Magda Tsolaki
  • Frans Verhey
  • Alberto Lléo
  • Isabel Sala
  • Julius Popp
  • Gwendoline Peyratout
  • Pablo Martinez-Lage
  • Mikel Tainta
  • Peter Johannsen
  • Yvonne Freund-Levi
  • Lutz Frölich
  • Valerija Dobricic
  • Cristina Legido-Quigley
  • Lars Bertram
  • Frederik Barkhof
  • Henrik Zetterberg
  • B Paul Morgan
  • Johannes Streffer
  • Pieter Jelle Visser
  • Simon Lovestone
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftJournal of Alzheimer's Disease
Vol/bind74
Udgave nummer1
Sider (fra-til)213-225
Antal sider13
ISSN1387-2877
DOI
StatusUdgivet - 2020

ID: 61377593