Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury

Amyloid beta-peptide, a major component of senile plaques in Alzheimer's disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer's disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid beta-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid beta-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 3 beta were significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid beta-peptide administration than those undergoing cerebral ischemia-reperfusion or amyloid beta-peptide administration alone. Conversely, the activity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid beta-peptide administration. These findings suggest that amyloid beta-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.