Jiang, YuanbingOrtiz Romero, Paula, 1994-Puig Pijoan, AlbertFernández-Lebrero, AidaContador, JoseSuárez-Calvet, MarcIp, Nancy Y.2024-09-252024-09-252024Jiang 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.136761552-5260http://hdl.handle.net/10230/61215Introduction: 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/alz.13676Alzheimer's diseaseAmyloid pathologyBlood biomarkersDisease stagingEarly detectionPatient stratificationPrecision medicineinfo:eu-repo/semantics/openAccess