AD发病机制的新探索:轴浆运输障碍假说

阿尔采末病(Alzheimer's disease,AD)是一种以老年斑、神经纤维缠结、突触密度减少和神经元丢失为主要病理改变的神经退行性疾病.目前对该病发病机制解释普遍接受的是淀粉样沉淀假说.而最新研究发现,早在β淀粉样多肽(Aβ)沉积和神经纤维缠结出现之前就有另一种病理改变,即轴突肿胀的出现.并且这一病理改变是由轴浆运输障碍引起的,最终可以导致Aβ沉积、突触功能障碍等其它AD相关的病理变化.据此推测,各种原因引起的轴浆运输障碍导致了AD的发病.本文通过介绍轴浆运输假说及其相关实验依据,对近年来AD发病机制的最新研究进展和尚待解决的问题作一综述.

A new hypothesis for early pathogenesis in Alzheimer's disease: impaired axonal transport mechanism

Alzheimer's disease (AD) is characterized by amyloid beta (Abeta) plaques and neurofibrillary tangles in the brain, reduced synaptic density, and progressive neuronal dysfunction and loss. The elevated levels of the Abeta peptides in brain likely associated to neurodegeneration and cognitive and behavioral abnormalities. While such amyloid mechanism contributes to Alzheimer's pathological conditions, recent studies from a number of laboratories suggest that defective axonal transport may represent an early stage in AD pathogenesis because axonal swellings and reduced axonal transport were observed before apparent AD hallmarks. Here, we overview recent findings that could compromise neuronal abnormalities and provide molecular and cellular insights into the potential mechanisms underlying the defective axonal transport. We also discuss issues to be addressed in future in elucidation of the complex cellular events involved in AD pathogenesis.