Changed Clathrin Regulatory Proteins in the Brains of Alzheimer's Disease Patients and Animal Models

In the study, the expression of clathrin regulatory proteins dynamin I, AP180, and synaptic vesicle protein synaptophysin in multiple brain regions of the patients with Alzheimer's disease (AD), the transgenic mice carrying the Swedish mutation of amyloid-beta protein precursor (A beta PP)670/671 (A beta PPSWE), and the rats injected by bilateral hippocampus with amyloid-beta peptide (A beta)(1-42) were examined by immunohistochemistry and Nissl staining, Western blotting, and Real-time PCR, respectively. Spatial learning and memory of the rats were evaluated by Morris Water Maze test, and the ability of endocytosis in the cultured rat hippocampal neurons was detected by FM1-43 fluorescence imaging. Significant decreases in protein levels of dynamin I, AP180, and synaptophysin were observed in both AD patients and mice with A beta PPSWE as compared to controls. Obvious declines of dynamin I and synaptophysin at protein and mRNA levels and impaired learning and spatial memory ability were found in the rats injected with A beta(1-42) as compared to controls. In addition, deposits of A beta localized in the hippocampus around the sites of A beta(1-42) injection and the decreased numbers of Nissl bodies in neurons were found. Moreover, the disrupted synaptic vesicle endocytosis and decreased dynamin I protein were detected in stimulated hippocampal neurons treated with A beta(1-42). These findings imply a malfunctioning clathrin-mediated endocytosis during AD pathological processes, which might be relevant to the mechanism underlying the cognitive deficit associated with AD.