CSF Biomarker Profile of Cerebral Amyloid Angiopathy: Diagnostic Performance and Imaging Correlates in a Hospital‐Based Neurology Cohort

ABSTRACT Background Cerebral amyloid angiopathy (CAA) frequently co‐occurs with Alzheimer's disease (AD), complicating diagnosis in patients with cognitive impairment. The CSF biomarker profile of CAA remains poorly understood, particularly with AD co‐pathology. We aimed to characterize CSF biomarkers in CAA, assess diagnostic accuracy, and examine associations with neuroimaging markers. Methods We included 261 participants from a hospital‐based cohort, recruited from memory clinic outpatients and neurology inpatients. Groups comprised healthy controls (HC, n = 35), CAA without AD co‐pathology (CAA‐nonAD, n = 27), CAA with AD co‐pathology (CAA‐AD, n = 30), and AD ( n = 169). CSF Aβ40, Aβ42, p‐tau181, and t‐tau were quantified using automated immunoassays. Group differences were tested using ANCOVA adjusted for age and sex. ROC analyses with 10‐fold cross‐validation and bootstrapping assessed diagnostic performance. Associations between CSF biomarkers and CAA‐related MRI markers were examined using ANCOVA. Results Aβ40 concentrations were lower in CAA‐nonAD and CAA‐AD compared to AD and HC ( p ‐value bf < 0.05). Aβ42 was reduced in CAA‐AD and AD versus HC, with no difference between CAA‐nonAD and AD. p‐tau181 and t‐tau were elevated in AD and CAA‐AD compared with CAA‐nonAD and HC ( p ‐value bf < 0.05). Aβ40 showed the highest diagnostic accuracy for CAA (AUC = 0.73; 95% CI: 0.66–0.80), followed by Aβ42 (AUC = 0.71; 95% CI: 0.64–0.78). In AD patients, Aβ42 best discriminated coexisting CAA (AUC = 0.77). Higher CAA‐SVD burden scores were associated with lower Aβ40 ( p ‐value bf < 0.05). Conclusions CSF Aβ40 and Aβ42 provide complementary diagnostic value for identifying CAA, both in isolation and with AD co‐pathology. Reduced Aβ40 is associated with greater CAA‐related vascular burden, supporting its role as a marker of vascular amyloid pathology.