Smith Karen D B, Peethumnongsin Erica, Lin Han, Zheng Hui, Pautler Robia G
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA.
Magn Reson Insights. 2010;4:11-18. doi: 10.4137/mri.s5237.
Amyloid precursor protein (APP) is implicated in axonal elongation, synaptic plasticity, and axonal transport. However, the role of APP on axonal transport in conjunction with the microtubule associated protein tau continues to be debated. Here we measured in vivo axonal transport in APP knockout mice with Manganese Enhanced MRI (MEMRI) to determine whether APP is necessary for maintaining normal axonal transport. We also tested how overexpression and mutations of tau affect axonal transport in the presence or absence of APP. In vivo axonal transport reduced significantly in the absence of functional APP. Overexpression of human wildtype tau maintained normal axonal transport and resulted in a transient compensation of axonal transport deficits in the absence of APP. Mutant R406Wtau in combination with the absence of APP compounded axonal transport deficits and these deficits persisted with age. These results indicate that APP is necessary for axonal transport, and overexpression of human wildtype tau can compensate for the absence of APP at an early age.
淀粉样前体蛋白（APP）与轴突伸长、突触可塑性和轴突运输有关。然而，APP与微管相关蛋白tau共同在轴突运输中的作用仍存在争议。在此，我们利用锰增强磁共振成像（MEMRI）测量APP基因敲除小鼠的体内轴突运输，以确定APP对维持正常轴突运输是否必要。我们还测试了在有或没有APP的情况下，tau的过表达和突变如何影响轴突运输。在缺乏功能性APP时，体内轴突运输显著减少。人类野生型tau的过表达维持了正常的轴突运输，并在没有APP的情况下导致轴突运输缺陷的短暂补偿。突变型R406W tau与缺乏APP共同作用加剧了轴突运输缺陷，且这些缺陷随年龄持续存在。这些结果表明，APP对轴突运输是必要的，并且人类野生型tau的过表达可以在早期弥补APP的缺失。
