Heterogeneous blood‐brain barrier dysfunction in cerebral small vessel diseases

作者：Yunqing Ying, Yingying Li, Tingyan Yao, Xingfeng Shao, Weijun Tang, Axel Montagne, Hugues Chabriat, Danny J.J. Wang, Chaodong Wang, Qi Yang, Xin Cheng · 发表于：Alzheimer s & Dementia · 年份：2024 · DOI：10.1002/alz.13874 · 被引用次数：38 · 研究领域：Cerebrovascular and genetic disorders、Neurological Disease Mechanisms and Treatments、Intracerebral and Subarachnoid Hemorrhage Research

Abstract INTRODUCTION We explored how blood‐brain barrier (BBB) leakage rate of gadolinium chelates (K trans ) and BBB water exchange rate (k w ) varied in cerebral small vessel disease (cSVD) subtypes. METHODS Thirty sporadic cSVD, 40 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and 13 high‐temperature requirement factor A serine peptidase 1 (HTRA) ‐related cSVD subjects were investigated parallel to 40 healthy individuals. Subjects underwent clinical, cognitive, and MRI assessment. RESULTS In CADASIL, no difference in K trans , but lower k w was observed in multiple brain regions. In sporadic cSVD, no difference in k w , but higher K trans was found in the whole brain and normal‐appearing white matter. In HTRA1‐related cSVD, both higher K trans in the whole brain and lower k w in multiple brain regions were observed. In each patient group, the altered BBB measures were correlated with lesion burden or clinical severity. DISCUSSION In cSVD subtypes, distinct alterations of k w and K trans were observed. The combination of K trans and k w can depict the heterogeneous BBB dysfunction. Highlights We measured BBB leakage to gadolinium‐based contrast agent (K trans ) and water exchange rate (k w ) across BBB in three subtypes of cSVD. CADASIL is characterized by lower k w , HTRA1‐related cSVD exhibits both higher K trans and lower k w , while sporadic cSVD is distinguished by higher K trans . There are distinct alterations ...