TY - JOUR
T1 - Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort
AU - Westwood, Sarah
AU - Baird, Alison L.
AU - Anand, Sneha N.
AU - Nevado-Holgado, Alejo J.
AU - Kormilitzin, Andrey
AU - Shi, Liu
AU - Hye, Abdul
AU - Ashton, Nicholas J.
AU - Morgan, Angharad R.
AU - Bos, Isabelle
AU - Vos, Stephanie J.B.
AU - Baker, Susan
AU - Buckley, Noel J.
AU - Ten Kate, Mara
AU - Scheltens, Philip
AU - Teunissen, Charlotte E.
AU - Vandenberghe, Rik
AU - Gabel, Silvy
AU - Meersmans, Karen
AU - Engelborghs, Sebastiaan
AU - De Roeck, Ellen E.
AU - Sleegers, Kristel
AU - Frisoni, Giovanni B.
AU - Blin, Olivier
AU - Richardson, Jill C.
AU - Bordet, Régis
AU - Molinuevo, José L.
AU - Rami, Lorena
AU - Wallin, Anders
AU - Kettunen, Petronella
AU - Tsolaki, Magda
AU - Verhey, Frans
AU - Lléo, Alberto
AU - Sala, Isabel
AU - Popp, Julius
AU - Peyratout, Gwendoline
AU - Martinez-Lage, Pablo
AU - Tainta, Mikel
AU - Johannsen, Peter
AU - Freund-Levi, Yvonne
AU - Frölich, Lutz
AU - Dobricic, Valerija
AU - Legido-Quigley, Cristina
AU - Bertram, Lars
AU - Barkhof, Frederik
AU - Zetterberg, Henrik
AU - Morgan, B. Paul
AU - Streffer, Johannes
AU - Visser, Pieter Jelle
AU - Lovestone, Simon
N1 - Funding Information:
This research was conducted as part of the EMIF-AD project which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n◦ 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. ANH and SL were supported by a MRC Mental Health Data Pathfinder award to the University of Oxford, and by the NIHR Oxford Health Biomedical Research Centre (BRC). FB is supported by the NIHR UCLH biomedical research centre. The Lausanne study was funded by a grant from the Swiss National Research Foundation (SNF 320030141179). Cardiff University acknowledge Wellcome Trust support (grant: 104025/Z/14/Z) as part of the research project entitled “Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer’s Disease”. The views expressed are those of the authors and not necessarily those of the MRC, the NHS, the NIHR or the Department of Health.
Publisher Copyright:
© 2020 - IOS Press and the authors. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/10
Y1 - 2020/3/10
N2 - 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 ϵ4 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.
AB - 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 ϵ4 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.
UR - http://www.scopus.com/inward/record.url?scp=85082024715&partnerID=8YFLogxK
U2 - 10.3233/JAD-190434
DO - 10.3233/JAD-190434
M3 - Journal articles
C2 - 31985466
AN - SCOPUS:85082024715
SN - 1387-2877
VL - 74
SP - 213
EP - 225
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -
