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

Alzheimer's & dementia : the journal of the Alzheimer's Association 2024

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.

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