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. 2011 Sep 29;27(5):287. doi: 10.1007/s12264-011-1736-7

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

Ai-Wu Xiao 1, Jing He 1, Qian Wang 1,2, Yi Luo 1, Yan Sun 1, Yan-Ping Zhou 1, Yang Guan 3, Paul J Lucassen 2, Jia-Pei Dai 1,✉
PMCID: PMC5560317  PMID: 21934724

Abstract

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 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 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.

Keywords: Alzheimer’s disease, axonopathy, senile plaques, neurofibrillary tangles, postmortem tracing

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