Cerebrospinal Fluid Amyloid-β Biomarkers Predict Future Hemorrhage in Patients with Cerebral Amyloid Angiopathy

Accurately predicting future hemorrhagic events in patients with cerebral amyloid angiopathy (CAA) remains a major clinical challenge. It is unknown whether cerebrospinal fluid (CSF) biomarkers of amyloid-beta (Aβ) pathology are associated with increased hemorrhage risk in this population.

We analyzed consecutive patients meeting Boston criteria version 2.0 for probable CAA with CSF Aβ data obtained during diagnostic workup. The primary outcome was incident intracranial hemorrhage, including lobar intracerebral, convexity subarachnoid, and non-traumatic subdural hemorrhage. Secondary outcomes were ischemic stroke and all-cause mortality. Associations between low CSF Aβ biomarkers and outcomes were analyzed using Cox proportional hazards models, adjusted for disseminated cortical superficial siderosis, and prior intracerebral hemorrhage.

Among 109 patients (median age: 77 years, 42% female), 16 (15%) experienced incident intracranial hemorrhage and 11 (10%) incident ischemic stroke during a median follow-up of 2.93 years (interquartile range: 1.43-5.03). In multivariate Cox regression models low CSF Aβ biomarkers were independently associated with incident intracranial hemorrhage (Aβ₄₀: hazard ratio: 8.04; [95% CI: 2.43-26.59], p < 0.001; Aβ₄₂: hazard ratio 7.10; [95% CI: 1.58-32.00], p = 0.011). CSF Aβ biomarkers were not associated with incident ischemic strokes and all-cause mortality. A composite risk score integrating low CSF Aβ biomarkers and hemorrhagic imaging features identified a high-risk subgroup with 78% hemorrhage incidence (7/9 patients) and a no-risk group without events (0/42 patients).

Low CSF Aβ biomarkers are independently associated with future symptomatic hemorrhage in CAA patients. A composite risk score may support individualized risk stratification and guide clinical decision-making. ANN NEUROL 2026;100:391-399.