The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer's disease
The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer's disease
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DOI：
10.1007/s12264-011-1736-7
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发表时间：
2011-10-01
影响因子：
5.6
通讯作者：
Dai, Jia-Pei
中科院分区：
文献类型：
--
作者：
Xiao, Ai-Wu;He, Jing;Dai, Jia-Pei
目的神经毒性β-淀粉样蛋白的产生和过度磷酸化tau蛋白的形成被认为是阿尔茨海默病（AD）神经病理机制的关键步骤。然而，关于它们在AD发病中的重要性仍然存在争议。最近的研究表明，轴突病变被认为是AD的早期阶段。然而，轴突病与经典神经病理学改变如老年斑（SP）和神经纤维缠结（NFT）的起源和发展之间的确切关系尚不清楚。本研究旨在探讨这种关系。方法采用死后追踪法，结合免疫组织化学或免疫荧光染色，观察轴突病变及SP和NFT的形成。结果“轴突漏”是一种新的轴突病，常伴有广泛的轴突肿胀和血管曲张，与AD患者脑内A β斑块和tau蛋白过度磷酸化的发生发展有关。结论轴索病变，尤其是轴索渗漏，可能是AD神经病理过程启动的关键事件。
Objective The production of neurotoxic beta-amyloid and the formation of hyperphosphorylated tau are thought to be critical steps contributing to the neuropathological mechanisms in Alzheimer's disease (AD). However, there remains an argument as to their importance in the onset of AD. Recent studies have shown that axonopathy is considered as an early stage of AD. However, the exact relationship between axonopathy and the origin and development of classic neuropathological changes such as senile plaques (SPs) and neurofibrillary tangles (NFTs) is unclear. The present study aimed to investigate this relationship. Methods Postmortem tracing, combined with the immunohistochemical or immunofluorescence staining, was used to detect axonopathy and the formation of SPs and NFTs. Results "Axonal leakage"-a novel type of axonopathy, was usually accompanied with the extensive swollen axons and varicosities, and was associated with the origin and development of A beta plaques and hyperphosphorylated tau in the brains of AD patients. Conclusion Axonopathy, particularly axonal leakage, might be a key event in the initiation of the neuropathological processes in AD.