Circulating Amyloid and Tau Biomarkers in Cerebral Amyloid Angiopathy: Insights from a single-center experience

Cerebral amyloid angiopathy (CAA) presents significant diagnostic challenges due to its overlap with other cerebrovascular and neurodegenerative conditions. This study investigated the clinical, cognitive, neuroradiologic, and plasma biomarker profiles of 58 patients diagnosed with probable or possible CAA, with 20 healthy controls for comparison. Our findings demonstrated that 69% of patients had probable CAA based on the Boston Criteria 2.0, with 27.6% showing mixed CAA and deep perforator arteriopathy features. Key symptoms included intracerebral hemorrhage (38.5%), cognitive decline (36%), and gait disturbances (13.5%). Neuroimaging revealed common features such as lobar microbleeds (84.2%) and white matter hyperintensities (68.4%). Plasma biomarkers indicated significantly lower Aβ 1-42 levels (p=0.002) and higher total tau concentrations (p=0.01) in CAA patients compared to controls, with a trend toward higher tau in cognitively impaired individuals (p=0.06). Cognitive decline correlated with medial temporal and global cortical atrophy, as measured by MoCA and TMT scores. Our study suggests that while circulating biomarkers may offer a less invasive alternative to CSF analysis for CAA diagnosis, they are not yet reliable for routine clinical use. Future work should explore comprehensive biomarker panels incorporating additional markers such as neurofilament light chain, phosphorylated tau, and APOE to improve diagnostic accuracy