Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation.

摘要: Neurofibrillary tangles (NFTs) and neuritic plaques (NPs) are two major histopathological lesions in Alzheimer's disease (AD). Although their aetiological relationship is unclear, both NFTs dystrophic neurites of NPs display immunoreactivity for ubiquitin. This suggests that dysfunction ubiquitin-mediated proteolysis the resulting accumulation ubiquitin-conjugated proteins may contribute to origination NFTs. We recently discovered a novel constituent neuropathological protein aggregates, ubiquitin-binding p62, with evidence p62 into cytoplasmic inclusions might be interconnected. In present work we examined detail role AD-type pathology, i.e. NFTs, neuropil threads. Using immunohistochemistry ubiquitin hyperphosphorylated tau, analysed parietal cortical samples 15 clinicopathologically verified AD cases nine nondemented aged subjects abundant NPs. found appears early during neurofibrillary pathogenesis invariably stably contrast, was absent or barely detectable Furthermore, NP-associated were generally devoid regardless content tau and/or The results suggest involvement critical aggregation perikaryal