TY - JOUR
T1 - Replication study of plasma proteins relating to Alzheimer's pathology
AU - Shi, Liu
AU - Winchester, Laura M.
AU - Westwood, Sarah
AU - Baird, Alison L.
AU - Anand, Sneha N.
AU - Buckley, Noel J.
AU - Hye, Abdul
AU - Ashton, Nicholas J.
AU - Bos, Isabelle
AU - Vos, Stephanie J. B.
AU - Kate, Mara ten
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, R. gis
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 - Barkhof, Frederik
AU - Andreasson, Ulf
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Streffer, Johannes
AU - Lill, Christina M.
AU - Bertram, Lars
AU - Visser, Pieter Jelle
AU - Kolb, Hartmuth C.
AU - Narayan, Vaibhav A.
AU - Lovestone, Simon
AU - Nevado-Holgado, Alejo J.
N1 - Funding Information: This research was conducted as part of the EMIF-AD MBD 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. 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). RV is a senior clinical investigator of the Flemish Research Foundation (FWO). 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). We 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. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532); the European Research Council (#681712); Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862); and the UK Dementia Research Institute at UCL. FB is supported by the NIHR biomedical research center at UCLH. Publisher Copyright: © 2021 the Alzheimer's Association Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9
Y1 - 2021/9
N2 - Introduction: This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the “ATN” (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis. Methods: Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively. Results: Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and “N” varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis. Discussion: Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
AB - Introduction: This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the “ATN” (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis. Methods: Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively. Results: Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and “N” varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis. Discussion: Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
KW - ATN framework
KW - Alzheimer's disease
KW - biomarker
KW - dementia
KW - network analysis
KW - plasma proteomics
KW - replication
UR - http://www.scopus.com/inward/record.url?scp=85103432126&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/alz.12322
DO - https://doi.org/10.1002/alz.12322
M3 - Article
C2 - 33792144
SN - 1552-5260
VL - 17
SP - 1452
EP - 1464
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 9
ER -