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

BACKGROUND Cerebral amyloid angiopathy (CAA) frequently co-occurs with Alzheimer’s disease (AD), which complicates diagnosis in patients with cognitive impairment. The cerebrospinal fluid (CSF) biomarker profile of CAA, particularly in the presence of AD co-pathology, remains poorly defined. We aimed to characterize CSF biomarkers in CAA, assess their diagnostic accuracy, and examine associations with neuroimaging markers of CAA. METHODS We included 261 participants from a hospital-based neurology cohort at Hospital del Mar (Barcelona, Spain), recruited from both memory-clinic outpatients (Cognitive and Behavioural Neurology Unit) and Neurology inpatients (including the Neurovascular Unit). 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 analysis of covariance adjusted for age and sex. Receiver operating characteristic (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, but did not differ between CAA-nonAD and AD. 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 in the presence of AD co-pathology. Reduced Aβ40 is associated with greater CAA-related vascular burden, supporting its role as a marker of vascular amyloid pathology.