Cerebrovascular lesions induce transient β-amyloid deposition

Monica Garcia-Alloza, Julia Gregory, Kishore V. Kuchibhotla, Sara Fine, Ying Wei, Cenk Ayata, Matthew P. Frosch, Steven M. Greenberg, Brian J. Bacskai

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3694-3704
Number of pages11
JournalBrain
Volume134
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

Keywords

  • Alzheimer's disease pathology
  • amyloid
  • stroke

ASJC Scopus subject areas

  • Clinical Neurology

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