Inhibition of axonal transport of hippocampal neurons by amyloid proteins: relation to Alzheimer's disease

点击翻译按钮获取中文摘要

Recent studies on Alzheimer's disease have suggested that β-amyloid protein is closely related to the pathogenesis of this disease. In the present study, the effect of β-amyloid protein on axonal transport of particles in neurites of cultured rat hippocampal neurons was investigated using video-enhanced microscopy. Application of β-amyolid protein_<25-35> (Aβ_<25-35>) rapidly decreased the number of particles transported in anterograde and retrograde directions. This effect was sustained during the application. When the concentration of Aβ_<25-35> was increased, the effect was irreversible and progressive. Axonal transport of mitochondria was also reduced. When Aβ_<25-35> was per fused intracellularly using patch pipettes, axonal transport was extremely reduced. The inhibitory effect of Aβ_<25-35> was blocked by the pre-treatment with butyrolactone I, a cyclin-dependent kinase 5 (Cdk5) to hyperphosphorylate tau proteins. These results indicate that β-amyloid protein inhibits axonal transport of particles including mitochondria. This effect may be induced by Cdk5-mediated phosphorylation of tau proteins. Reduction in axonal transport by β-amyloid protein may be related to the pathogenesis of Alzheimer's disease.