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Cleavage of amyloid precursor protein elicited by chronic cerebral hypoperfusion
S A Bennett1, B A Pappas, W D Stevens
1Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, KIH 8M5, Ottawa, ON, Canada. bennett@aix1.uottawa.ca
Abstract:
In the present study, we sought to determine whether low-grade, chronic vascular insufficiency induced in a rodent model of chronic cerebrohypoperfusion is sufficient, in and of itself, to trigger cleavage of the amyloid precursor protein (APP) into beta A-sized fragments. We report that chronic two vessel occlusion (2VO) results in progressive accumulation of beta A peptides detected by Western analysis in aged rats correlating with a shift in the immunohistochemical localization of APP from neurons to extracellular deposits in brain parenchyma. These data indicate that the 2VO paradigm reproduces features of beta A biogenesis characteristic of sporadic Alzheimer's disease.