Cerebrovascular lesions induce transient -amyloid deposition
- 25 November 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Brain
- Vol. 134 (12), 3697-3707
- https://doi.org/10.1093/brain/awr300
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.This publication has 65 references indexed in Scilit:
- Antioxidants have a rapid and long-lasting effect on neuritic abnormalities in APP:PS1 miceNeurobiology of Aging, 2010
- Matrix metalloproteinase inhibition reduces oxidative stress associated with cerebral amyloid angiopathy in vivo in transgenic miceJournal of Neurochemistry, 2009
- A γ‐secretase inhibitor decreases amyloid‐β production in the central nervous systemAnnals of Neurology, 2009
- Contribution of Vascular Risk Factors to the Progression in Alzheimer DiseaseArchives of Neurology, 2009
- Aβ Plaques Lead to Aberrant Regulation of Calcium Homeostasis In Vivo Resulting in Structural and Functional Disruption of Neuronal NetworksNeuron, 2008
- Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s diseaseNature, 2008
- Hypertension and the Risk of Mild Cognitive ImpairmentArchives of Neurology, 2007
- Depletion of GGA3 Stabilizes BACE and Enhances β-Secretase ActivityNeuron, 2007
- AD brain pathology: Vascular origins?Neurobiology of Aging, 2007
- Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expressionProceedings of the National Academy of Sciences of the United States of America, 2006