Polygenic risk score predicts pathologically confirmed cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) both involve amyloid beta (Aβ) accumulation in vessels and brain parenchyma, respectively. As Aβ-targeting therapies emerge, CAA draws attention due to its link with amyloid-related imaging abnormalities (ARIA), underscoring the need for biomarkers beyond magnetic resonance imaging (MRI).

CAA polygenic risk scores (CAA-PRS) were generated in 105 ADNI participants, and their predictive ability for pathological CAA was evaluated, including in subgroups with high amyloid burden or without MRI-visible CAA markers.

CAA-PRS was significantly associated with pathological CAA (OR = 1.766, p < 0.001), with an AUC of 0.783 overall and 0.766 (OR = 1.780, p = 0.002) in those with high amyloid burden. A marginal association was observed in MRI-negative individuals.

CAA-PRS may serve as a complementary biomarker to imaging for identifying high-risk individuals with CAA, particularly in the context of Aβ-targeting therapies and ARIA risk.

CAA-PRS is generated. CAA-PRS is associated with pathologically confirmed CAA. CAA-PRS is associated with CAA in individuals with high amyloid burden.