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ID 115647
タイトル別表記
Raft-derived tau-associated vesicles
著者
Nishikawa, T. Hiroshima University
Takahashi, T. Hiroshima University
Nakamori, M. Hiroshima University
Hosomi, N. Hiroshima University
Maruyama, H. Hiroshima University
Matsumoto, M. Hiroshima University
キーワード
Alzheimer’s disease
granulovacuolar degeneration
lipid raft
pretangle
signaling endosome
tau
資料タイプ
学術雑誌論文
抄録
Aims: Neurofibrillary tangles (NFTs), a cardinal pathological feature of neurodegenerative disorders, such as Alzheimer's disease (AD) are primarily composed of hyper‐phosphorylated tau protein. Recently, several other molecules, including flotillin‐1, phosphatidylinositol‐4,5‐bisphosphate [PtdIns(4,5)P2] and cyclin‐dependent kinase 5 (CDK5), have also been revealed as constituents of NFTs. Flotillin‐1 and PtdIns(4,5)P2 are considered markers of raft microdomains, whereas CDK5 is a tau kinase. Therefore, we hypothesized that NFTs have a relationship with raft domains and the tau phosphorylation that occurs within NFTs. Methods: We investigated six cases of AD, six cases of other neurodegenerative diseases with NFTs and three control cases. We analysed the PtdIns(4,5)P2‐immunopositive material in detail, using super‐resolution microscopy and electron microscopy to elucidate its pattern of expression. We also investigated the spatial relationship between the PtdIns(4,5)P2‐immunopositive material and tau kinases through double immunofluorescence analysis. Results: Pretangles contained either paired helical filaments (PHFs) or PtdIns(4,5)P2‐immunopositive small vesicles (approximately 1 μm in diameter) with nearly identical topology to granulovacuolar degeneration (GVD) bodies. Various combinations of these vesicles and GVD bodies, the latter of which are pathological hallmarks observed within the neurons of AD patients, were found concurrently in neurons. These vesicles and GVD bodies were both immunopositive not only for PtdIns(4,5)P2, but also for several tau kinases such as glycogen synthase kinase‐3β and spleen tyrosine kinase. Conclusions: These observations suggest that clusters of raft‐derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase‐bearing vesicles are likely involved in the modification of tau protein and in NFT formation.
掲載誌名
Neuropathology and Applied Neurobiology
ISSN
13652990
cat書誌ID
AA00754798
出版者
British Neuropathological Society|John Wiley & Sons
42
7
開始ページ
639
終了ページ
653
発行日
2015-10-26
権利情報
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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言語
eng
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部局
病院