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), 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-valuebf < 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-valuebf < 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-valuebf < 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.