Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay
Number of Authors: 532019 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 11, p. 1478-1488Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 15, no 11, p. 1478-1488
Keywords [en]
Amyloid beta, SOMAscan assay, Plasma proteomics, Replication, Causal relationship, Tau
National Category
Neurology
Identifiers
URN: urn:nbn:se:oru:diva-78371DOI: 10.1016/j.jalz.2019.06.4951ISI: 000496951600011PubMedID: 31495601Scopus ID: 2-s2.0-85071719989OAI: oai:DiVA.org:oru-78371DiVA, id: diva2:1374896
Note
Funding Agencies:
Innovative Medicines Initiative Joint Undertaking under EMIF grant 115372
European Union (EU)
EFPIA companies'
European Commission Joint Research Centre QLRT-2001-245537670
Stichting voor Alzheimer Onderzoek 11020 13007 15005
Department of Health of the Basque Government 17.0.1.08.12.0000.2.454.01.41142.001.H
University of Antwerp Research Fund
NIHR biomedical research centre at UCLH
DPUK through MRC MR/L023784/2
Medical Research Council UK (MRC) MC_PC_17215
2019-12-032019-12-032023-03-28Bibliographically approved