@article{9b34d3a1056d4b24879054dfda3b883f,
title = "Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay",
abstract = "Introduction: Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins.Methods: 4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid.Results: A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) e4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization.Discussion: The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition. (C) 2019 The Authors. Published by Elsevier Inc.",
keywords = "Amyloid beta, SOMAscan assay, Plasma proteomics, Replication, Causal relationship, Tau, BLOOD-BASED BIOMARKERS, ALZHEIMERS-DISEASE, MENDELIAN RANDOMIZATION, CASCADE HYPOTHESIS, SIGNALING PATHWAYS, MARKERS, TAU, MODELS, DRUG, AGE",
author = "Liu Shi and Sarah Westwood and Baird, {Alison L.} and Laura Winchester and Valerija Dobricic and Fabian Kilpert and Shengjun Hong and Andre Franke and Abdul Hye and Ashton, {Nicholas J.} and Morgan, {Angharad R.} and Isabelle Bos and Vos, {Stephanie J. B.} and Buckley, {Noel J.} and {ten Kate}, Mara and Philip Scheltens and Rik Vandenberghe and Silvy Gabel and Karen Meersmans and Sebastiaan Engelborghs and {De Roeck}, {Ellen E.} and Kristel Sleegers and Frisoni, {Giovanni B.} and Olivier Blin and Richardson, {Jill C.} and Regis Bordet and Molinuevo, {Jose L.} and Lorena Rami and Anders Wallin and Petronella Kettunen and Magda Tsolaki and Frans Verhey and Alberto Lleo and Daniel Alcolea and Julius Popp and Gwendoline Peyratout and Pablo Martinez-Lage and Mikel Tainta and Peter Johannsen and Teunissen, {Charlotte E.} and Yvonne Freund-Levi and Lutz Froelich and Cristina Legido-Quigley and Frederik Barkhof and Kaj Blennow and Henrik Zetterberg and Susan Baker and Morgan, {B. Paul} and Johannes Streffer and Visser, {Pieter Jelle} and Lars Bertram and Simon Lovestone and Nevado-Holgado, {Alejo J.}",
note = "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 no. 115372 , resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013), and EFPIA companies' in-kind contribution. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the 5th framework program (contract # 37670 ). The Leuven cohort was funded by the Stichting voor Alzheimer Onderzoek (grant numbers #11020, #13007, and #15005). R.V. is a senior clinical investigator of the Flemish Research Foundation (FWO). J.S. is currently an employee of UCB, Braine-l{\textquoteright}Alleud, Belgium. The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). The authors acknowledge the contribution of the personnel of the Genomic Service Facility at the VIB-U Antwerp Center for Molecular Neurology. The research at VIB-CMN is funded in part by the University of Antwerp Research Fund. F.B. is supported by the NIHR biomedical research centre at UCLH. L.S. is funded by DPUK through MRC (grant no. MR/L023784/2 ) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215 ). 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 no. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013), and EFPIA companies' in-kind contribution. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the 5th framework program (contract # 37670). The Leuven cohort was funded by the Stichting voor Alzheimer Onderzoek (grant numbers #11020, #13007, and #15005). R.V. is a senior clinical investigator of the Flemish Research Foundation (FWO). J.S. is currently an employee of UCB, Braine-l'Alleud, Belgium. The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). The authors acknowledge the contribution of the personnel of the Genomic Service Facility at the VIB-U Antwerp Center for Molecular Neurology. The research at VIB-CMN is funded in part by the University of Antwerp Research Fund. F.B. is supported by the NIHR biomedical research centre at UCLH. L.S. is funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215). Authors' contributions: S.W. A.L.B. and S.L. contributed to study concept and design, and all authors contributed to sample collection/selection and/or interpretation of data. L.S. and A.J.N.-H. carried out data analysis and interpretation. L.S. drafted the manuscript, and all authors revised the manuscript. Ethics statement: Written informed consent was obtained from all participants before inclusion in the study. The medical ethics committee at each site approved the study. Data availability: The data sets generated and analyzed during the present study are available via the EMIF-AD Catalogue via submitted research questions, which have to be approved by the data-owners from each parent cohort Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = nov,
doi = "10.1016/j.jalz.2019.06.4951",
language = "English",
volume = "15",
pages = "1478--1488",
journal = "Alzheimer's & Dementia",
issn = "1552-5260",
publisher = "Elsevier Science",
number = "11",
}