Affiliations: [a] Department of Pathology, the First Clinical Hospital of Harbin Medical University, Harbin 150001, China | [b] Department of Pathology, Chinese Hospital of Mudanjiang, Mudanjiang 157000, China | [c] Department of Pathology, the Second Affiliated Hospital of Tsinghua University, Beijing 100049, China
Note: [1] These authors contributed equally to this study.
Note: [] Communicated by Dengshun Wang
Abstract: Growing evidence suggests a synergistic and perhaps etiological relationship between vascular disease and Alzheimer's disease (AD), which is characterized by the progressive accumulation of amyloid-β peptide (Aβ). Moreover, apolipoprotein E (ApoE) has also been shown to be associated with AD and cerebral ischemia. It seems that cerebral ischemia may play an important, both direct and indirect, role in the pathogenesis of AD. We investigated the expression and distribution of Aβ1–40, β1–42 and ApoE in human hippocampus after cerebral ischemia in this study to determine the role of cerebral ischemia in Alzheimer's disease. Our study has demonstrated that the accumulation of both Aβ1–40 and β1–42 were increased dramatically and consistently after cerebral ischemia. Neuronal ApoE immunoreactivity was also significantly increased in all ischemic groups compared with controls. The most likely stimulus for the increased Aβ1–40, Aβ1–42 and ApoE immunoreactivity in the CA1 and CA3 neurons is the ischemic conditions, and their upregulation, in turn, may partly explain the contribution of cerebral ischemia to the pathogenesis of AD. Therefore our observations provide a basis for establishing therapeutic strategies aimed at preventing ischemic insults and subsequent neurodegeneration in AD.
Keywords: Cerebral ischemia, amyloid-β, apolipoprotein E, Alzheimer's disease, human hippocampus
