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Alzheimer's Disease, Other Dementia, Aging

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Raft derived vesicles are another component of neurofibrillary tangle

  • P2-291
  • 中森 正博 / Masahiro Nakamori:1,2 高橋 哲也 / Tetsuya Takahashi:1 西川 智和 / Tomokazu Nishikawa:1 松原 知康 / Tomoyasu Matsubara:1 李 成玉 / Chengyu Li:1 篠崎 ゆかり / Yukari Shinozaki:1 永野 義人 / Yoshito Nagano:1 丸山 博文 / Hirofumi Maruyama:1 松本 昌泰 / Masayasu Matsumoto:1 
  • 1:広島大院医歯薬脳神経内科 / Dept Neurol, Univ of Hiroshima, Hiroshima, Japan 2:翠清会梶川病院 / Dept Neurol, Suiseikai Kajikawa Hospital, Hiroshima, Japan 

Introduction: Alzheimer's disease (AD) brain pathologically manifests amyloid plaques and neurofibrillary tangles (NFTs), Granulovacuolar degeneration (GVD) bodies are also pathological hallmarks of AD. We reported that GVD bodies are immunopositive for charged multivesicular body protein 2B (CHMP2B), suggesting that GVD body is the structure related to multivesicular body (MVB). We also reported that both cyclin dependent kinase 5, one of tau kinases and lipid raft marker such as phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] exist not only in GVD bodies but also in NFTs. These results suggest that conversion of raft derived vesicle toward MVB have particular relation to both GVD and NFT.
Material and Methods: Brain specimens from five AD cases and 17 other neurodegenerative disease cases and four control cases were subjected to double staining of immunohistochemical technique, using anti-PtdIns(4,5)P2, anti-CHMP2B, anti-RD3, anti-RD4, anti-flotillin-1 antibodies and Gallyas-Braak method. In addition, we investigated the relationship between the number of GVD bodies and the area of PtdIns(4,5)P2 positive vesicles within individual neuron in the CA1 at every GVD stage. Moreover, we observed the hippocampus of AD using electron microscopy to investigate vesicular structure within NFT.
Results: PtdIns(4,5)P2 positive small vesicles were located in close proximity to tau immunoreactivity. Gallyas-Braak method revealed that these vesicles existed in pretangle. We also observed that paired helical filaments were intermingled with these vesicles using electron microscopy. Statistical analysis showed the number of GVD bodies and the area of PtdIns(4,5)P2 positive structures were inversely correlated.
Conclusion: We identified the raft derived small vesicles within pretangle. These vesicles are likely to provide a platform to modify tau as signaling endosome.

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