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- W2113996052 abstract "Evidence of a substantial vascular component to the pathogenesis Alzheimer's disease (AD) has converged from multiple sources, in vivo, epidemiologic and clinicopathologic studies. We find substantial evidence of degenerated capillaries and associated areas of small vessel leakage, haemorrhage and micro-scar formation. These micro-infarcts coincide with ßA plaques and, importantly, are foci of degenerating neurites. They can be staged based on presence of soluble factors and blood cells, and glial reactivity. The lesions occur in clusters relating to feeding and draining vessel, most frequently adjacent to branch points. Their occurrence appears to be chronic in that clusters of resolved infarcts are interspersed with newer, more active lesions. The two key questions were to define a) where along the microvascular network do the lesions occur b) what is the chronologic pattern of infarcts in brain regions and c) do vascular risk factors correlate with anatomic locations and chronology of the lesions. We analysed post mortem brain from 30 cases with a range of AD lesion density using markers of haemorrhage, microglial activation, blood vessels and ischaemia. Microvascular degeneration coincides with the progression of the classic AD lesions. We methodically defined this microvascular breakdown anatomically and propose a mechanism for the chronicity of the microvascular breakdown using markers of infarct age in post mortem tissue from well defined cohorts of patients with and without vascular-related risk factors. The clustering of capillary degeneration, microbleeds, inflammation, and iron compounds were spatially related to the microvascular architecture. The lesion age could be determined by the level of microglial activity and inflammatory profile. Recent and resolved lesions occurred in clusters. This analysis was used to model the propagation of microinfarts across time and brain region." @default.
- W2113996052 created "2016-06-24" @default.
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- W2113996052 date "2010-07-01" @default.
- W2113996052 modified "2023-09-27" @default.
- W2113996052 title "P2-350: Inflammation and resolution of the plaque ischaemic penumbra" @default.
- W2113996052 doi "https://doi.org/10.1016/j.jalz.2010.05.1401" @default.
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