Fluid biomarkers in Cerebral amyloid angiopathy: current limitations and future directions

Introduction Cerebral amyloid angiopathy (CAA) is the leading cause of lobar intracerebral hemorrhage in older adults and an independent contributor to cognitive decline. Current diagnostic criteria are based on neuroimaging, lacking pathophysiological specificity.Areas covered This narrative review evaluated studies assessing cerebrospinal fluid (CSF) and plasma biomarkers in sporadic CAA compared with Alzheimer disease (AD), other small vessel diseases, and healthy controls (HC). CSF profiles show reduced beta-amyloid 1–42 and beta-amyloid 1–42/ beta-amyloid 1–40 ratio in CAA, although a similar pattern is observed in AD, limiting the specificity of these markers. Beta-amyloid 1–40 is decreased in CAA versus HC and AD, reflecting vascular amyloid deposition, yet this alteration alone does not provide sufficient discriminatory power. Plasma studies have reported heterogeneous results, influenced by variability in methods and populations studied. Nevertheless, amyloid isoforms and phosphorylated tau appear promising. Neurofilament light chain has been linked to imaging markers and disease burden, though prognostic data remain scarce.Given the frequent coexistence of CAA and AD, the limited pathophysiological specificity of current neuroimaging criteria, and the growing therapeutic implications of accurate diagnosis, interest in fluid biomarkers has increased substantially in recent years.Expert opinion Currently, fluid biomarkers lack both specificity and validation required for clinical implementation in CAA, largely due to substantial overlap with AD pathology. Their clinical utility remains unproven, and large longitudinal real-world studies are needed to assess their reliability and incremental diagnostic value.