A blood-based multi-pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups

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• dc.contributor.author Jiang, Yuanbing
• dc.contributor.author Ortiz Romero, Paula, 1994-
• dc.contributor.author Puig Pijoan, Albert
• dc.contributor.author Fernández-Lebrero, Aida
• dc.contributor.author Contador, Jose
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Ip, Nancy Y.
• dc.date.accessioned 2024-09-25T05:58:01Z
• dc.date.available 2024-09-25T05:58:01Z
• dc.date.issued 2024
• dc.description.abstract Introduction: Existing blood-based biomarkers for Alzheimer's disease (AD) mainly focus on its pathological features. However, studies on blood-based biomarkers associated with other biological processes for a comprehensive evaluation of AD status are limited. Methods: We developed a blood-based, multiplex biomarker assay for AD that measures the levels of 21 proteins involved in multiple biological pathways. We evaluated the assay's performance for classifying AD and indicating AD-related endophenotypes in three independent cohorts from Chinese or European-descent populations. Results: The 21-protein assay accurately classified AD (area under the receiver operating characteristic curve [AUC] = 0.9407 to 0.9867) and mild cognitive impairment (MCI; AUC = 0.8434 to 0.8945) while also indicating brain amyloid pathology. Moreover, the assay simultaneously evaluated the changes of five biological processes in individuals and revealed the ethnic-specific dysregulations of biological processes upon AD progression. Discussion: This study demonstrated the utility of a blood-based, multi-pathway biomarker assay for early screening and staging of AD, providing insights for patient stratification and precision medicine. Highlights: The authors developed a blood-based biomarker assay for Alzheimer's disease. The 21-protein assay classifies AD/MCI and indicates brain amyloid pathology. The 21-protein assay can simultaneously assess activities of five biological processes. Ethnic-specific dysregulations of biological processes in AD were revealed.
• dc.description.sponsorship This study was supported in part by the National Key R&D Program of China (2021YFE0203000); the Areas of Excellence Scheme of the University Grants Committee (AoE/M-604/16); the Research Grants Council of Hong Kong (the Collaborative Research Fund [C6027-19GF] and the Theme-Based Research Scheme [T13-605/18 W]); the Innovation and Technology Commission (InnoHK; ITCPD/17-9, INNOHK18SC01, ITS/207/18FP, MRP/042/18X, and MRP/097/20X); Chow Tai Fook Charity Foundation (CTFCF18SC01); the Guangdong Provincial Key S&T Program Grant (2018B030336001); the Guangdong Provincial Fund for Basic and Applied Basic Research (2019B1515130004); and the Fundamental Research Program of Shenzhen Virtual University Park (2021Szvup137). Yuanbing Jiang is a recipient of the Hong Kong Postdoctoral Fellowship Award from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKUST PDFS2324-6S04). Marc Suárez-Calvet received funding from the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (Grant Agreement No. 948677); Project “PI19/00155,” co-funded by Instituto de Salud Carlos III (ISCIII) and the European Union; and a fellowship from “La Caixa” Foundation (ID 100010434); and a fellowship from the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement (No. 847648; LCF/BQ/PR21/11840004). Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2022-01018 and #2019-02397), the European Union's Horizon Europe Research and Innovation Programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme—Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003).
• dc.format.mimetype application/pdf
• dc.identifier.citation Jiang Y, Uhm H, Ip FC, Ouyang L, Lo RMN, Cheng EYL, et al. A blood-based multi-pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups. Alzheimers Dement. 2024 Mar;20(3):2000-15. DOI: 10.1002/alz.13676
• dc.identifier.doi http://dx.doi.org/10.1002/alz.13676
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/61215
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Alzheimers Dement. 2024 Mar;20(3):2000-15
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948677
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847648
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101053962
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/860197
• dc.rights © 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Alzheimer's disease
• dc.subject.keyword Amyloid pathology
• dc.subject.keyword Blood biomarkers
• dc.subject.keyword Disease staging
• dc.subject.keyword Early detection
• dc.subject.keyword Patient stratification
• dc.subject.keyword Precision medicine
• dc.title A blood-based multi-pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion