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This study examined blood-brain barrier dysfunction in cerebral amyloid angiopathy (CAA) by measuring the CSF/serum albumin quotient (QAlb) in 225 participants. Researchers found that QAlb levels were significantly elevated in CAA patients compared to both healthy controls and Alzheimer's disease patients, and pathological QAlb levels were independently associated with disseminated cortical superficial siderosis, a marker indicating high risk for future brain hemorrhage. The findings suggest that blood-brain barrier breakdown, measurable through routine fluid biomarkers, may identify patients with the most dangerous hemorrhage-prone form of CAA.
Why it matters
This research identifies a readily available clinical marker (QAlb) that could help clinicians identify CAA patients at highest risk for life-threatening brain hemorrhages, potentially enabling more targeted monitoring and treatment strategies. The findings strengthen understanding of how vascular barrier dysfunction contributes to hemorrhagic complications in CAA.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background: Blood-brain barrier (BBB) dysfunction is increasingly recognized as a feature of cerebral amyloid angiopathy (CAA) and has been linked to hemorrhagic imaging manifestations such as cortical superficial siderosis. However, it remains unclear whether neurovascular barrier dysfunction can be captured by routinely available fluid biomarkers and whether such markers identify clinically relevant hemorrhage-prone CAA phenotypes. The CSF/serum albumin quotient (QAlb) is an established marker of neurovascular barrier dysfunction. We investigated QAlb levels in CAA and their association with imaging markers of disease severity. Methods: We included 225 participants (115 with CAA, 72 with Alzheimers disease [AD], 38 healthy controls) with CSF biomarkers and standardized MRI evaluation. Pathologic QAlb levels were identified via the age-corrected Reiber-formula. Group differences and determinants of pathological QAlb were assessed using uni- and multivariable regression analyses. The diagnostic relevance was assessed by receiver operating characteristic analysis. Results: QAlb levels were higher in CAA than in controls (ratio of means [RoM] 1.43, 95% CI 1.28-1.58) and patients with AD (RoM 1.22, 95% CI 1.10-1.35; both p<0.001). Pathological QAlb was independently associated with CAA compared with controls (OR 12.16, 95% CI 2.56-57.86) and AD (OR 2.14, 95% CI 1.07-4.28). Despite these associations, QAlb showed only moderate discrimination between CAA and controls (AUC 0.75, 95% CI 0.67-0.82) and low discrimination between CAA and AD (AUC 0.63, 95% CI 0.55-0.71). Within the CAA cohort, pathological QAlb was independently associated with disseminated cortical superficial siderosis (OR 3.92, 95% CI 1.31-11.72; p=0.014), a marker of advanced hemorrhage-prone disease. Conclusion: QAlb is elevated in patients with CAA and is associated with disseminated cortical superficial siderosis, the strongest predictor of future intracerebral hemorrhage. These findings support an association between neurovascular barrier dysfunction and the hemorrhage-prone phenotype of CAA.