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- Title
Cerebrovascular lesions induce transient β-amyloid deposition.
- Authors
Garcia-Alloza, Monica; Gregory, Julia; Kuchibhotla, Kishore V; Fine, Sara; Wei, Ying; Ayata, Cenk; Frosch, Matthew P; Greenberg, Steven M; Bacskai, Brian J
- Abstract
Previous clinical studies have documented a close relationship between cerebrovascular disease and risk of Alzheimer's disease. We examined possible mechanistic interactions through use of experimental stroke models in a transgenic mouse model of β-amyloid deposition (APPswe/PS1dE9). Following middle cerebral artery occlusion, we observed a rapid increase in amyloid plaque burden in the region surrounding the infarction. In human tissue samples, however, we were unable to detect a localized increase in amyloid burden adjacent to cerebral infarcts. To resolve this discrepancy, we generated cerebral microstrokes in amyloid precursor protein mouse models with the photosensitive dye Rose bengal, and monitored plaque formation in real time using multiphoton microscopy. We observed a striking increase in the number of new plaques and amyloid angiopathy in the area immediately surrounding the infarcted area; however, the effect was transient, potentially resolving the discord between mouse and human tissue. We did not detect changes in candidate proteins related to β-amyloid generation or degradation such as β-amyloid-converting enzyme, amyloid precursor protein, presenilin 1, neprylisin or insulin-degrading enzyme. Together, these results demonstrate that strokes can trigger accelerated amyloid deposition, most likely through interference with amyloid clearance pathways. Additionally, this study indicates that focal ischaemia provides an experimental paradigm in which to study the mechanisms of plaque seeding and growth.
- Publication
Brain : a journal of neurology, 2011, Vol 134, Issue Pt 12, p3697
- ISSN
1460-2156
- Publication type
Journal Article
- DOI
10.1093/brain/awr300