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

Neurosci Bull. 2011 Oct;27(5):287-99. doi: 10.1007/s12264-011-1736-7.

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.

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-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。

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Axonal Transport
  • Axons / metabolism
  • Axons / pathology*
  • Brain / metabolism
  • Brain / pathology*
  • Brain / ultrastructure
  • Case-Control Studies
  • Female
  • Frontal Lobe / metabolism
  • Frontal Lobe / pathology
  • Frontal Lobe / ultrastructure
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / ultrastructure
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Neuroanatomical Tract-Tracing Techniques / methods
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Plaque, Amyloid / pathology*
  • Postmortem Changes
  • Reference Values
  • Temporal Lobe / metabolism
  • Temporal Lobe / pathology
  • Temporal Lobe / ultrastructure
  • Tissue Banks
  • tau Proteins / metabolism*

Substances

  • tau Proteins