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Distinct microglial response against Alzheimer’s amyloid and tau pathologies characterized by P2Y12 receptor
https://repo.qst.go.jp/records/81529
https://repo.qst.go.jp/records/815298d610ce5-38f4-4211-a921-d1d5de3e35e7
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-01-05 | |||||
| タイトル | ||||||
| タイトル | Distinct microglial response against Alzheimer’s amyloid and tau pathologies characterized by P2Y12 receptor | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Maeda, Jun
× Maeda, Jun× Minamihisamatsu, Takeharu× Shimojo, Masafumi× Xiaoyun, Zhou× Ono, Maiko× Matsuba, Yukio× Ji, Bin× Ishii, Hideki× Ogawa, Masanao× Akatsu, Hiroyasu× Kaneda, Daita× Hashizume, Yoshio× L. Robinson, John× Virginia, M-Y Lee× Saito, Takashi× C. Saido, Takaomi× Q. Trojanowski, John× Ming-Rong, Zhang× Suhara, Tetsuya× Higuchi, Makoto× Sahara, Naruhiko× Jun, Maeda× Takeharu, Minamihisamatsu× Masafumi, Shimojo× Xiaoyun, Zhou× Maiko, Ono× Ji, Bin× Hideki, Ishii× Masanao, Ogawa× Zhang, Ming-Rong× Tetsuya, Suhara× Makoto, Higuchi× Naruhiko, Sahara |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Microglia are the resident phagocytes of the central nervous system, and microglial activation is considered to play an important role in the pathogenesis of neurodegenerative diseases. Recent studies with single-cell RNA analysis of CNS cells in Alzheimer’s disease (AD) and diverse other neurodegenerative conditions revealed that the transition from homeostatic microglia to disease-associated microglia (DAM) was defined by changes of gene expression levels, including down-regulation of the P2Y12 receptor (P2Y12R). However, it is yet to be clarified in AD brains whether and when this down-regulation occurs in response to amyloid-β (Aβ) and tau depositions, which are core pathological processes in the disease etiology. To further evaluate the significance of P2Y12R alterations in the neurodegenerative pathway of AD and allied disorders, we generated an anti-P2Y12R antibody and examined P2Y12R expressions in the brains of humans and model mice bearing Aβ and tau pathologies. We observed that the brains of both AD and non-AD tauopathy patients and tauopathy model mice (rTg4510 and PS19 mouse lines) displayed declined microglial P2Y12R levels in regions enriched with tau inclusions, despite an increase in the total microglial population. Notably, diminution of microglial immunoreactivity with P2Y12R was noticeable prior to massive accumulations of phosphorylated tau aggregates and neurodegeneration in rTg4510 mouse brains, despite a progressive increase of total microglial population. On the other hand, Iba1-positive microglia encompassing compact and dense-cored Aplaques expressed P2Y12R at varying levels in amyloid precursor protein (APP) mouse models (APP23 and AppNL-F/NL-F mice). By contrast, neuritic plaques in AD brains were associated with P2Y12R-negative microglia. These data suggest that the down-regulation of microglia P2Y12R, which is characteristic of DAM, is intimately associated with tau rather than Aβ pathologies from an early stage and could be a sensitive index for neuroinflammatory responses to AD-related neurodegenerative processes. | |||||
| 書誌情報 |
Brain Communications 巻 3, 号 1, p. fcab011, 発行日 2021-01 |
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| 出版者 | ||||||
| 出版者 | Oxford University Press | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2632-1297 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 33644757 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1093/braincomms/fcab011 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://academic.oup.com/braincomms/article/3/1/fcab011/6123787 | |||||
