Cerebrospinal Fluid Amyloid‐β Biomarkers Predict Future Hemorrhage in Patients with Cerebral Amyloid Angiopathy
OBJECTIVE: 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. METHODS: 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. RESULTS: : 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). INTERPRETATION: 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.
Authors
- Eya Khadhraoui (ORCID: https://orcid.org/0000-0002-5433-1572)
- Valentina Perosa (ORCID: https://orcid.org/0000-0002-3551-5237)
- Philipp Arndt (ORCID: https://orcid.org/0000-0002-0517-6473)
- Malte Pfister
- Cornelia Garz
- Hendrik Mattern (ORCID: https://orcid.org/0000-0001-5740-4522)
- Marc Dörner (ORCID: https://orcid.org/0000-0003-3229-1677)
- Sebastian J. Müller
- Johanna Engel
- Katja Neumann
- Melis Taş
- Marwa Al‐Dubai
- Patrick Müller
- Lara Holzheimer
- Stefanie Schreiber
- Sven G. Meuth
Institutions
- German Center for Neurodegenerative Diseases (DE)
- Massachusetts General Hospital (US)
- University Hospital of Zurich (CH)
- Center for Behavioral Brain Sciences (DE)
- Heinrich Heine University Düsseldorf (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- Annals of Neurology
- Published
- 2026-04-27
- DOI
- https://doi.org/10.1002/ana.78241
- Primary Topic
- Intracerebral and Subarachnoid Hemorrhage Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00