Département de pathologie et biologie cellulaire, Université de Montréal, Montréal, QC, Canada.
Eur J Neurosci. 2013 Jun;37(12):1939-48. doi: 10.1111/ejn.12229.
It is well documented that neurofibrillary tangles composed of aggregated tau protein propagate in a predictable pattern in Alzheimer's disease (AD). The mechanisms underlying the propagation of tau pathology are still poorly understood. Recent studies have provided solid data demonstrating that in several neurodegenerative diseases including AD, the spreading of misfolded protein aggregates in the brain would result from prion-like cell-to-cell transmission. Consistent with this new concept, recent studies have reported that human tau can be released in the extracellular space by an active process of secretion, and can be endocytosed both in vitro and in vivo. Most importantly, it was reported that the spreading of tau pathology was observed along synaptically connected circuits in a transgenic mouse model where human tau overexpression was restricted in the entorhinal cortex. This indicates that secretion of tau by presynaptic neurons and its uptake by postsynaptic neurons could be the sequential events leading to the propagation of tau pathology in the brain.
有大量文献记载，阿尔茨海默病（AD）中聚集的tau 蛋白组成的神经原纤维缠结以可预测的模式传播。tau 病理学传播的机制仍知之甚少。最近的研究提供了确凿的数据，证明在包括 AD 在内的几种神经退行性疾病中，错误折叠的蛋白质聚集体在大脑中的传播是由类朊病毒样的细胞间传播引起的。与这一新概念一致，最近的研究报告称，人类 tau 可以通过主动分泌过程释放到细胞外空间，并且可以在体外和体内被内吞。最重要的是，据报道，在人类 tau 过度表达仅限于内侧隔核的转基因小鼠模型中，tau 病理学的传播沿着突触连接的回路发生。这表明，突触前神经元分泌 tau 和突触后神经元摄取 tau 可能是导致大脑中 tau 病理学传播的连续事件。
