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.
Original language | English |
---|---|
Pages (from-to) | 1478-1488 |
Number of pages | 11 |
Journal | Alzheimer's & Dementia |
Volume | 15 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2019 |
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
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- 10.1016/j.jalz.2019.06.4951Licence: CC BY
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In: Alzheimer's & Dementia, Vol. 15, No. 11, 11.2019, p. 1478-1488.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay
AU - Shi, Liu
AU - Westwood, Sarah
AU - Baird, Alison L.
AU - Winchester, Laura
AU - Dobricic, Valerija
AU - Kilpert, Fabian
AU - Hong, Shengjun
AU - Franke, Andre
AU - Hye, Abdul
AU - Ashton, Nicholas J.
AU - Morgan, Angharad R.
AU - Bos, Isabelle
AU - Vos, Stephanie J. B.
AU - Buckley, Noel J.
AU - ten Kate, Mara
AU - Scheltens, Philip
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, Regis
AU - Molinuevo, Jose L.
AU - Rami, Lorena
AU - Wallin, Anders
AU - Kettunen, Petronella
AU - Tsolaki, Magda
AU - Verhey, Frans
AU - Lleo, Alberto
AU - Alcolea, Daniel
AU - Popp, Julius
AU - Peyratout, Gwendoline
AU - Martinez-Lage, Pablo
AU - Tainta, Mikel
AU - Johannsen, Peter
AU - Teunissen, Charlotte E.
AU - Freund-Levi, Yvonne
AU - Froelich, Lutz
AU - Legido-Quigley, Cristina
AU - Barkhof, Frederik
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Baker, Susan
AU - Morgan, B. Paul
AU - Streffer, Johannes
AU - Visser, Pieter Jelle
AU - Bertram, Lars
AU - Lovestone, Simon
AU - Nevado-Holgado, Alejo J.
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 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 ). 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: © 2019 The Authors
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
KW - Amyloid beta
KW - SOMAscan assay
KW - Plasma proteomics
KW - Replication
KW - Causal relationship
KW - Tau
KW - BLOOD-BASED BIOMARKERS
KW - ALZHEIMERS-DISEASE
KW - MENDELIAN RANDOMIZATION
KW - CASCADE HYPOTHESIS
KW - SIGNALING PATHWAYS
KW - MARKERS
KW - TAU
KW - MODELS
KW - DRUG
KW - AGE
U2 - 10.1016/j.jalz.2019.06.4951
DO - 10.1016/j.jalz.2019.06.4951
M3 - Article
C2 - 31495601
SN - 1552-5260
VL - 15
SP - 1478
EP - 1488
JO - Alzheimer's & Dementia
JF - Alzheimer's & Dementia
IS - 11
ER -