In probable CAA, lower CSF Aβ40 and Aβ42 levels are associated with established MRI markers of disease severity, independently of clinical presentation and concomitant Alzheimer-like profile, suggesting that CSF Aβ levels may reflect vascular amyloid burden rather than downstream neurodegeneration.
Lower CSF Aβ40 levels were significantly associated with greater cortical superficial siderosis (cSS) burden in probable CAA.
Lower CSF Aβ42 levels were significantly associated with greater cortical superficial siderosis (cSS) burden in probable CAA.
Lower CSF Aβ40 levels were significantly associated with higher Fazekas score (white matter hyperintensity burden) in probable CAA.
Lower CSF Aβ42 levels were significantly associated with higher Fazekas score in probable CAA.
Neither CSF Aβ40 nor Aβ42 levels were significantly associated with lobar cerebral microbleed (CMB) count.
No significant association was found between CSF tau species (total tau or p-tau181) and any MRI markers of disease severity.
The study cohort consisted of 102 patients with probable CAA diagnosed according to Boston criteria v2.0 at two tertiary centers between 2014 and 2023.
Associations between CSF Aβ levels and MRI severity markers remained significant after stratification by CSF Aβ42/Aβ40-defined Alzheimer-like profile.
Cerebral amyloid angiopathy (CAA) is a condition where a protein called amyloid builds up in the walls of blood vessels in the brain, leading to bleeding and other types of brain damage. It is currently diagnosed using MRI brain scans, but these scans show the damage that has already occurred rather than directly measuring the disease process itself. This study examined whether proteins measured in cerebrospinal fluid (the fluid surrounding the brain and spinal cord) could provide a more direct window into how severe CAA has become. Specifically, researchers looked at levels of amyloid-beta proteins (Aβ40 and Aβ42) and tau proteins in 102 patients with probable CAA. This research suggests that lower levels of both Aβ40 and Aβ42 in cerebrospinal fluid are linked to more severe signs of CAA on MRI, specifically more cortical superficial siderosis (a type of iron deposit from prior bleeding on the brain's surface) and greater white matter damage. Notably, these fluid biomarkers were not associated with the number of tiny brain bleeds called microbleeds, which are the primary marker used to diagnose CAA on MRI. Tau proteins, which are associated with Alzheimer's disease and nerve cell death, showed no meaningful association with any MRI severity markers. Importantly, the associations between low amyloid-beta levels and MRI severity held even when accounting for whether patients also had Alzheimer's-like changes in their fluid biomarkers. These findings matter because they suggest that measuring amyloid-beta proteins in cerebrospinal fluid could offer a complementary tool for assessing how advanced CAA is, beyond what MRI alone can show. The fact that tau proteins were not associated with disease severity, while amyloid-beta proteins were, supports the idea that low fluid amyloid-beta reflects amyloid being trapped in blood vessel walls rather than general brain cell damage. The authors call for future studies that follow patients over time to determine whether these fluid biomarkers can predict how the disease will progress.
Beaufort Q, Charbonnier C, Ruellan P, Ozkul-Wermester O, Amar V, Turpin D, et al.. (2026). Evaluation of Disease Severity Using CSF Biomarkers in Patients With Probable Cerebral Amyloid Angiopathy.. Neurology. https://doi.org/10.1212/WNL.0000000000218458