Background and purposeCerebrovascular parenchymal damage is prevalent in ageing brains; however, its vascular aetiology has not been fully elucidated. In addition to the underlying role of sclerotic arterioles, the correlation between collagenised venules has not been clarified. Here, we aimed to investigate the associations between microvascular injuries, including arteriolosclerosis and venular collagenosis, and related parenchymal damages in ageing brains, to investigate the underlying correlations.MethodsWe evaluated arteriolosclerosis and venular collagenosis in 7 regions from 27 autopsy cases with no history of stroke or brain tumour. The correlations between the ratio of arteriolosclerosis, venular collagenosis and the severity of cerebrovascular parenchymal damage, including lacunes, microinfarcts, myelin loss, and parenchymal and perivascular haemosiderin deposits, were assessed.ResultsArteriolosclerosis and venular collagenosis became more evident with age. Arteriolosclerosis was associated with lacunes (p=0.004) and brain parenchymal haemosiderin deposits in the superior frontal cortex (p=0.024) but not with leukoaraiosis severity. Venular collagenosis was not associated with the number of lacunes or haemosiderin, while white matter generally became paler with severe venular collagenosis in the periventricular (β=−0.430, p=0.028) and deep white matter (β=−0.437, p=0.025).ConclusionOur findings imply an important role for venular lesions in relation to microvessel-related parenchymal damage which is different from that for arteriolosclerosis. Different underlying mechanisms of both cerebral arterioles and venules require further investigation.
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.
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