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.
