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

Jiang Y, Uhm H, Ip FC, Ouyang L, Lo RMN, Cheng EYL, Cao X, Tan CMC, Law BCH, Ortiz-Romero P, Puig-Pijoan A, Fernández-Lebrero A, Contador J, Mok KY, Hardy J, Kwok TCY, Mok VCT, Suárez-Calvet M, Zetterberg H, Fu AKY, Ip NY

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.

Keywords: Alzheimer's disease; amyloid pathology; blood biomarkers; disease staging; early detection; patient stratification; precision medicine.

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Reference

Jiang Y, Uhm H, Ip FC, Ouyang L, Lo RMN, Cheng EYL, Cao X, Tan CMC, Law BCH, Ortiz-Romero P, Puig-Pijoan A, Fernández-Lebrero A, Contador J, Mok KY, Hardy J, Kwok TCY, Mok VCT, Suárez-Calvet M, Zetterberg H, Fu AKY, Ip NY. A blood-based multi-pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups. Alzheimers Dement. 2024 Jan 6. doi: 10.1002/alz.13676. Epub ahead of print. PMID: 38183344.