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

Journal article
Authors 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
Published in Journal of Alzheimer's disease : JAD
Volume 74
Issue 1
Pages 213-225
ISSN 1875-8908
Publication year 2020
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Wallenberg Centre for Molecular and Translational Medicine
Pages 213-225
Language en
Links dx.doi.org/10.3233/JAD-190434
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Neurosciences

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.

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