Circulating proteomic biomarkers for cerebral amyloid angiopathy screening and risk stratification

INTRODUCTION: We systematically characterized plasma protein profiles in cerebral amyloid angiopathy (CAA) using proteomics and identified a hub protein panel for disease diagnosis and risk stratification. METHODS: A total of 146 patients with probable CAA and 128 community-dwelling controls were prospectively enrolled. Plasma samples underwent proteomic analysis, and the hub proteins were validated in two validation cohorts. Machine learning algorithms were applied to construct and validate the performance of the circulating panel. RESULTS: We identified 166 differentially expressed proteins in patients with CAA. Six hub proteins were selected to form the circulating panel, demonstrating excellent performance to distinguish patients from controls in all cohorts. Additionally, the risk stratification system derived from the hub protein panel accurately identified patients at high risk for new-onset lobar intracerebral hemorrhage. DISCUSSION: Our findings revealed distinctive circulating protein signatures in CAA and established a validated hub protein panel aiding in CAA screening and risk stratification. HIGHLIGHTS: We identified plasma protein signatures in CAA using proteomics. A circulating hub protein panel was developed and validated, demonstrating high accuracy for disease screening. The hub protein panel effectively stratified CAA patients according to risk of future intracerebral hemorrhage. The circulating panel offers potential for CAA screening and risk stratification.