Cleavage of amyloid precursor protein elicited by chronic cerebral hypoperfusion

In the present study, we sought to determine whether low-grade, chronic vas cular insufficiency induced in a rodent model of chronic cerebrohypoperfusi on is sufficient, in and of itself, to trigger cleavage of the amyloid prec ursor protein (APP) into beta A-sized fragments. We report that chronic two vessel occlusion (2VO) results in progressive accumulation of beta A pepti des detected by Western analysis in aged rats correlating with a shift in t he immunohistochemical localization of APP from neurons to extracellular de posits in brain parenchyma. These data indicate that the 2VO paradigm repro duces features of beta A biogenesis characteristic of sporadic Alzheimer's disease. (C) 2000 Elsevier Science Inc. All rights reserved.