Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA Department of Psychiatry, New York University School of Medicine, NY, USA.
J Alzheimers Dis. 2013;37(3):579-86. doi: 10.3233/JAD-130671.
Microtubule-based axonal transport is believed to become globally disrupted in Alzheimer's disease in part due to alterations of tau expression or phosphorylation. We previously showed that axonal transport rates along retinal ganglion axons are unaffected by deletion of normal mouse tau or by overexpression of wild-type human tau. Here, we report that htau mice expressing 3-fold higher levels of human tau in the absence of mouse tau also display normal fast and slow transport kinetics despite the presence of abnormally hyperphosphorylated tau in some neurons. In addition, markers of slow transport (neurofilament light subunit) and fast transport (snap25) exhibit normal distributions along optic axons of these mice. These studies demonstrate that human tau overexpression, even when associated with a limited degree of tau pathology, does not necessarily impair general axonal transport function in vivo.
基于微管的轴突运输被认为在阿尔茨海默病中会全面受损，部分原因是由于 tau 表达或磷酸化的改变。我们之前曾表明，视网膜神经节轴突的轴突运输速率不受正常小鼠 tau 的缺失或野生型人 tau 的过表达的影响。在这里，我们报告说，在没有小鼠 tau 的情况下表达 3 倍以上人 tau 的 htau 小鼠也表现出正常的快速和慢速运输动力学，尽管在一些神经元中存在异常过度磷酸化的 tau。此外，在这些小鼠的视神经轴突中，慢速运输标志物（神经丝轻链）和快速运输标志物（snap25）表现出正常的分布。这些研究表明，即使与人 tau 病理程度有限相关，人 tau 的过表达也不一定会损害体内的一般轴突运输功能。
