Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Science. 2010 Oct 8;330(6001):198. doi: 10.1126/science.1194653. Epub 2010 Sep 9.
Amyloid-β (Aβ) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer's disease (AD). How exactly they impair cognitive functions is unknown. We assessed the effects of Aβ and tau on axonal transport of mitochondria and the neurotrophin receptor TrkA, cargoes that are critical for neuronal function and survival and whose distributions are altered in AD. Aβ oligomers rapidly inhibited axonal transport of these cargoes in wild-type neurons. Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, Aβ requires tau to impair axonal transport, and tau reduction protects against Aβ-induced axonal transport defects.
淀粉样蛋白-β（Aβ）肽来源于淀粉样前体蛋白，微管相关蛋白 tau 是阿尔茨海默病（AD）的关键致病因素。它们究竟如何损害认知功能尚不清楚。我们评估了 Aβ和 tau 对线粒体和神经营养因子受体 TrkA 的轴突运输的影响，这些货物对神经元功能和存活至关重要，其分布在 AD 中发生改变。Aβ 低聚物在野生型神经元中迅速抑制这些货物的轴突运输。降低 tau 水平可防止这些缺陷而不影响基线轴突运输。因此，Aβ需要 tau 来损害轴突运输，而 tau 的减少可防止 Aβ 诱导的轴突运输缺陷。
