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Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.

Authors :
Shi L
Westwood S
Baird AL
Winchester L
Dobricic V
Kilpert F
Hong S
Franke A
Hye A
Ashton NJ
Morgan AR
Bos I
Vos SJB
Buckley NJ
Kate MT
Scheltens P
Vandenberghe R
Gabel S
Meersmans K
Engelborghs S
De Roeck EE
Sleegers K
Frisoni GB
Blin O
Richardson JC
Bordet R
Molinuevo JL
Rami L
Wallin A
Kettunen P
Tsolaki M
Verhey F
Lleó A
Alcolea D
Popp J
Peyratout G
Martinez-Lage P
Tainta M
Johannsen P
Teunissen CE
Freund-Levi Y
Frölich L
Legido-Quigley C
Barkhof F
Blennow K
Zetterberg H
Baker S
Morgan BP
Streffer J
Visser PJ
Bertram L
Lovestone S
Nevado-Holgado AJ
Source :
Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2019 Nov; Vol. 15 (11), pp. 1478-1488. Date of Electronic Publication: 2019 Sep 05.
Publication Year :
2019

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.<br />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.<br />Results: 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.<br />Discussion: The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1552-5279
Volume :
15
Issue :
11
Database :
MEDLINE
Journal :
Alzheimer's & dementia : the journal of the Alzheimer's Association
Publication Type :
Academic Journal
Accession number :
31495601
Full Text :
https://doi.org/10.1016/j.jalz.2019.06.4951