Cleavage of amyloid precursor protein elicited by chronic cerebral hypoperfusion

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 βA-sized fragments. We report that chronic two vessel occlusion (2VO) results in progressive accumulation of βA 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 βA biogenesis characteristic of sporadic Alzheimer’s disease.