Histopathological Analysis of Cerebral Microvasculature Pathology with Alzheimer’s Disease Neuropathological Changes: An Autopsy Study

Background: Cerebrovascular lesions are associated with cognitive impairment. However, the implication of Alzheimer’s disease (AD) neuropathological changes (ADNC) on cerebral microvasculature is not completely understood. This study aimed to investigate the changes in the median tunica and basement membrane-related extracellular matrix (ECM) contents of the microvasculature and correlate this finding between the ADNC-impaired individuals and healthy controls. Methods: : In this study, 12 decedents with high or intermediate ADNC and 15 matched controls without ADNC were selected from a local brain bank. Tissue blocks were systematically collected from white matter regions of the cortex, putamen, and hippocampus. The proportions of small vessels affected by arteriolosclerosis and venular collagenosis, and the levels of collagen IV, laminin, fibronectin, perlecan, and agrin in the ECM were quantified by immunohistochemistry and compared between the two groups. Results: : Venular collagenosis was significantly more severe in AD patients than in controls across all selected brain regions ( p < 0.001 for all regions). Although arteriolosclerosis was substantially severe in the AD group, only arteriolosclerosis in putamen was significantly more severe (0.63 vs. 0.42, p = 0.040). Similar correlation patterns were observed between these changes in the media tunica and specific AD pathology scores. We found that the levels of collagen IV and fibronectin were decreased and agrin was increased in AD cases, showing that changes in ECM components were significantly correlated with ADNC. Conclusions: : Our data indicate that venular injuries with severe collagenosis in the media tunica and significant basement membrane-related ECM changes are important contributors to ADNC, providing potential new targets for investigation.