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Research Article

轴突病变可能通过阿尔茨海默氏症小鼠模型的轴突泄漏机制启动神经病理过程

卷 19, 期 3, 2019

页: [183 - 195] 页: 13

弟呕挨: 10.2174/1566524019666190405174908

价格: $65

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摘要

背景：过度磷酸化tau的形成和β-淀粉样蛋白的产生被认为是导致阿尔茨海默病（AD）病理机制的关键步骤。然而，关于它们在AD发病时的重要性存在长期争论。最近的研究表明，轴突病变被认为是AD的早期神经病理学改变。然而，轴突病变的发展与老年斑（SP）和神经原纤维缠结（NFTs）等典型神经病理学变化之间的确切关系尚不清楚。 目的：本研究旨在探讨SPs和NFTs的形成是否与轴突渗漏的发展有关。 方法和结果：在这里我们表明，轴突渗漏的形成和发展 - 一种新的轴突病变是一个年龄依赖的过程，伴随着轴突和静脉曲张的肿胀，并与昆明小鼠硫胺素缺乏（TD）饮食诱导的慢性氧化应激有关。在AD的APP / PS1转基因小鼠模型中，轴突渗漏出现在3个月，在6个月时变得更明显，并且在1个月后变得更严重。我们还表明轻微的轴突渗漏与过度磷酸化tau的形成有关，但与斑块没有关系，只有严重的轴突渗漏伴有广泛肿胀的轴突和静脉曲张，β-淀粉样蛋白的过量产生导致SP的形成和过度磷酸化的tau 。 结论：这些数据解释了SP和NFT的共同起源和发展，并提示轴突渗漏可能是AD发生神经病理过程的关键事件。

关键词: 轴突，轴突渗漏，老年斑，神经原纤维缠结，阿尔茨海默病。

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