Discovery and validation of plasma proteomic biomarkers relating tobrain amyloid burden by SOMAscan assay

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  • dc.contributor.author Shi, Liu
  • dc.contributor.author Molinuevo, José Luis
  • dc.contributor.author Nevado-Holgado, Alejo J.
  • dc.date.accessioned 2023-01-17T09:09:10Z
  • dc.date.available 2023-01-17T09:09:10Z
  • dc.date.issued 2019
  • dc.description.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.
  • dc.description.sponsorship 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).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Shi L, Westwood S, Baird AL, Winchester L, Dobricic V, Kilpert F, et al. Discovery and validation of plasma proteomic biomarkers relating tobrain amyloid burden by SOMAscan assay. Alzheimer's & Dementia. 2019 Nov;15(11):1478-88. DOI: 10.1016/j.jalz.2019.06.4951
  • dc.identifier.doi http://dx.doi.org/10.1016/j.jalz.2019.06.4951
  • dc.identifier.issn 1552-5260
  • dc.identifier.uri http://hdl.handle.net/10230/55301
  • dc.language.iso eng
  • dc.publisher Wiley
  • dc.relation.ispartof Alzheimer's & Dementia. 2019 Nov;15(11):1478-88
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115372
  • dc.rights ©2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer’s Association. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Amyloid β
  • dc.subject.keyword Causal relationship
  • dc.subject.keyword Plasma proteomics
  • dc.subject.keyword Replication
  • dc.subject.keyword SOMAscan assay
  • dc.subject.keyword Tau
  • dc.title Discovery and validation of plasma proteomic biomarkers relating tobrain amyloid burden by SOMAscan assay
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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