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Replication study of plasma proteins relating to Alzheimer's pathology
Department of Psychiatry, University of Oxford, Oxford, UK.
Örebro University, School of Medical Sciences. Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK; Karolinska Institutet Center for Alzheimer Research, Division of Clinical Geriatrics, Stockholm, Sweden; Department of Neurobiology, Caring Sciences and Society (NVS), Stockholm, Sweden.ORCID iD: 0000-0001-6863-6679
Department of Psychiatry, University of Oxford, Oxford, UK.
Number of Authors: 512021 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 17, no 9, p. 1452-1464Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2021. Vol. 17, no 9, p. 1452-1464
Keywords [en]
ATN framework, Alzheimer's disease, biomarker, dementia, network analysis, plasma proteomics, replication
National Category
Clinical Laboratory Medicine
Identifiers
URN: urn:nbn:se:oru:diva-90976DOI: 10.1002/alz.12322ISI: 000636452200001PubMedID: 33792144Scopus ID: 2-s2.0-85103432126OAI: oai:DiVA.org:oru-90976DiVA, id: diva2:1543916
Funder
Swedish Research Council, 2018-02532
Note

Funding Agencies:

Innovative Medicines Initiative Joint Undertaking under EMIF grant from the European Union's Seventh Framework Programme (FP7/2007-2013) 115372

European Commission Joint Research Centre QLRT-2001-2455 37670

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  

European Research Council (ERC) European Commission 681712

Swedish State Support for Clinical Research ALFGBG720931

Alzheimer Drug Discovery Foundation (ADDF), USA 201809-2016862

UK Dementia Research Institute at UCL  

NIHR biomedical research center at UCLH  

EFPIA companies'  

Available from: 2021-04-13 Created: 2021-04-13 Last updated: 2023-03-28Bibliographically approved

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Freund-Levi, Yvonne

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