The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease  

阿尔茨海默病老年斑及磷酸化tau蛋白的形成和发展与轴突病变相关(英文)

作　　者：肖爱武[1] 何敬[1] 王茜[1,2] 罗艺[1] 孙燕[1] 周艳平[1] 官阳[3] Paul J.Lucassen 戴甲培[1] 

机构地区：[1]中南民族大学武汉神经科学和神经工程研究所,武汉430074 [2]阿姆斯特丹大学生命科学研究所神经科学研究中心 [3]华中科技大学同济医学院病理学系超微病理研究室,武汉430030

出　　处：《Neuroscience Bulletin》2011年第5期287-299,共13页神经科学通报（英文版）

基　　金：supported by an"Excellent Project"of the China Ministry of Human Resources for Return Overseas Chinese Scholarship;partly by the Research Foundation for"Key Laboratory of Neu-roscience and Neuroengineering"of South-Central University for Nationalities(No.XJS09001);the National Natural Science Foundation of China(No.31070961)

摘　　要：Objective The production of neurotoxic β-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 immunofluo-rescence 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 Aβ 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.目的神经毒性β-淀粉样蛋白沉积和tau蛋白过度磷酸化是阿尔茨海默病(Alzheimer’s disease,AD)神经病理机制的两个关键阶段,然而关于它们在启动AD病程的重要性上仍存在争议。最近研究显示,轴突病变发生于AD的早期,然而轴突病变与老年斑(senile plaques,SPs)和神经纤维缠结(neurofibrillary tangles,NFTs)的发生发展之间的确切关系仍不清楚,本研究旨在揭示它们之间的联系。方法运用神经示踪技术结合免疫组织化学、免疫组织化学和免疫荧光双标技术,研究AD患者大脑中的轴突病变以及SPs和NFTs的形成情况。结果 AD患者的脑组织中呈现出一种新形式的轴突病变——"轴突漏",并伴随有大量肿胀的轴突和膨体。此外,轴突漏与β-淀粉样蛋白沉积和tau蛋白过度磷酸化的形成及发展有关。结论轴突病变尤其是"轴突漏"可能是起始AD神经病理进程的一个关键事件。

关 键 词：Alzheimer’s disease AXONOPATHY senile plaques neurofibrillary tangles postmortem tracing 

分 类 号：R749.16[医药卫生—神经病学与精神病学]