Core CSF Biomarker Profile in Cerebral Amyloid Angiopathy

BACKGROUND AND OBJECTIVES: There is a clear need to characterize and validate molecular biomarkers of cerebral amyloid angiopathy (CAA), in an effort to improve diagnostics, especially in the context of patients with Alzheimer disease (AD) receiving immunotherapies (for whom underlying CAA is the driver of amyloid-related imaging abnormalities). We performed an updated meta-analysis of 5 core CSF biomarkers (Aβ42, Aβ40, Aβ438, total tau T-tau, and phosphorylated tau P-tau) to assess which of these are most altered in sporadic CAA. METHODS: We systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting APP metabolism (Aβ42, Aβ40, Aβ38), neurodegeneration (T-tau), and tangle pathology (P-tau), in symptomatic sporadic CAA cohorts (based on the Boston criteria) vs control groups and/or vs patients with AD. Biomarker performance was assessed in random-effects meta-analysis based on ratio of mean (RoM) biomarker concentrations in (1) patients with CAA to controls and (2) CAA to patients with AD. RoM >1 indicates higher biomarker concentration in CAA vs comparison population, and RoM <1 indicates higher concentration in comparison groups. RESULTS: < 0.0001), respectively. DISCUSSION: Specific CSF patterns of Aβ42, Aβ40, Aβ38, T-tau, and P-tau might serve as molecular biomarkers of CAA, in research and clinical settings, offering the potential to improve the clinical diagnostic approach pathway in specific scenarios.