1. Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay
- Author
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Isabelle Bos, Henrik Zetterberg, Daniel Alcolea, Gwendoline Peyratout, B. Paul Morgan, Susan Baker, Simon Lovestone, Liu Shi, Fabian Kilpert, Lars Bertram, Shengjun Hong, Ellen Elisa De Roeck, Alberto Lleó, Mikel Tainta, Pablo Martinez-Lage, Kaj Blennow, Alison L. Baird, Olivier Blin, Lorena Rami, José Luis Molinuevo, Kristel Sleegers, Yvonne Freund-Levi, Lutz Frölich, Angharad R. Morgan, Pieter Jelle Visser, Rik Vandenberghe, Philip Scheltens, Silvy Gabel, Charlotte E. Teunissen, Petronella Kettunen, Julius Popp, Jill C. Richardson, Noel J. Buckley, Stephanie J. B. Vos, Abdul Hye, Johannes Streffer, Sarah Westwood, Nicholas J. Ashton, Valerija Dobricic, Alejo J. Nevado-Holgado, Magda Tsolaki, Giovanni B. Frisoni, Andre Franke, Frans R.J. Verhey, Sebastiaan Engelborghs, Mara ten Kate, Régis Bordet, Cristina Legido-Quigley, Laura Winchester, Anders Wallin, Karen Meersmans, Frederik Barkhof, Peter Johannsen, University of Oxford, Universität zu Lübeck = University of Lübeck [Lübeck], Christian-Albrechts University of Kiel, King‘s College London, University of Gothenburg (GU), Cardiff University, Maastricht University [Maastricht], VU University Medical Center [Amsterdam], University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Vrije Universiteit Brussel (VUB), University of Antwerp (UA), Université de Genève = University of Geneva (UNIGE), Istituto Centro San Giovanni di Dio Fatebenefratelli, Partenaires INRAE, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), CHU Lille, Université de Lille, Hospital Clinic (IDIBAPS), Universitat Pompeu Fabra [Barcelona] (UPF), Sahlgrenska Academy at University of Gothenburg [Göteborg], AHEPA University General Hospital [Thessaloniki], Hospital de la Santa Creu i Sant Pau, Lausanne University Hospital, Geneva University Hospital (HUG), Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián], Copenhagen University Hospital, Amsterdam UMC - Amsterdam University Medical Center, Vrije Universiteit Amsterdam [Amsterdam] (VU), Karolinska Institutet [Stockholm], Örebro University, Universität Heidelberg [Heidelberg] = Heidelberg University, Institutes of Neurology and Healthcare Engineering, UCL, London, Sahlgrenska University Hospital [Gothenburg], UCL, Institute of Neurology [London], Janssen Research & Development, University of Oslo (UiO), Neurology, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurodegeneration, Clinical chemistry, Faculty of Arts and Philosophy, Clinical sciences, Educational Science, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, Promovendi MHN, and MUMC+: MA Med Staf Spec Psychiatrie (9)
- Subjects
0301 basic medicine ,Apolipoprotein E ,Male ,Proteomics ,Neurology ,Epidemiology ,Apolipoprotein E4 ,Disease ,SOMAscan assay ,ddc:616.89 ,BLOOD-BASED BIOMARKERS ,0302 clinical medicine ,CASCADE HYPOTHESIS ,MARKERS ,Tau ,Medicine ,Biomarker discovery ,DRUG ,Medicine(all) ,Health Policy ,Age Factors ,Brain ,Middle Aged ,Blood proteins ,3. Good health ,Europe ,ALZHEIMERS-DISEASE ,Psychiatry and Mental health ,MENDELIAN RANDOMIZATION ,Biomarker (medicine) ,Female ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Amyloid ,MODELS ,Clinical Neurology ,Replication ,Plasma proteomics ,Computational biology ,Article ,SIGNALING PATHWAYS ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,AGE ,Developmental Neuroscience ,Alzheimer Disease ,Amyloid β ,Causal relationship ,Mendelian randomization ,Humans ,Biology ,Aged ,Science & Technology ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,Amyloid beta ,030104 developmental biology ,Neurology (clinical) ,Human medicine ,Neurosciences & Neurology ,Geriatrics and Gerontology ,TAU ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
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. 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. A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ε4, 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. The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition. 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 VIBCMN 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).
- Published
- 2019