CSF biomarkers of reactive glial cells are associated with blood–brain barrier leakage and white matter lesions

Cerebral small vessel disease (CSVD) is a prevalent cerebrovascular disease characterized by chronic vascular dysfunction [1], primarily diagnosed using MRI-based markers such as white matter hyperintensities (WMHs), cerebral microbleeds, perivascular spaces, and lacunes [2]. CSVD also involves blood–brain barrier (BBB) disruption, evident with an elevated cerebrospinal fuid (CSF)/serum albumin ratio (also called Albumin Quotient, QAlb) [3]. Despite these markers refecting different aspects of cerebrovascular disease, its underlying causes are not fully understood. Interestingly, CSVD often coincides with Alzheimer’s disease (AD) pathology [4], and abnormal tau pathology afects brain vessel architecture and worsens white matter neurite density [5]. More importantly, glial cell-mediated neuroinfammation is involved in the onset and progression of both CSVD and AD [6]. However, it is unclear whether the contribution of neuroinfammation to cerebrovascular injury is independent of AD pathology and the association between CSF biomarkers of reactive glial cells and CSVD features remains unknown.