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論文
- タイトル
- タイトル（英）
- A next-generation iPSC-derived forebrain organoid model of tauopathy with tau fibrils by AAV-mediated gene transfer.
- 参照URL
- https://researchmap.jp/shimozawaaki/published_papers/46011643
- 著者
- 著者（英）
- Hiroko Shimada,Yuta Sato,Takashi Sasaki,Aki Shimozawa,Kent Imaizumi,Tomoko Shindo,Sachiyo Miyao,Kosuke Kiyama,Takahiro Kondo,Shinsuke Shibata,Seiji Ishii,Junro Kuromitsu,Hirofumi Aoyagi,Daisuke Ito,Hideyuki Okano
- 担当区分
- 概要
- 概要（英）
- It is known that the human cellular models of Alzheimer's disease (AD) and tauopathy can only recapitulate the very early stage of the disease. To overcome these limitations, we developed a technology to make forebrain organoids (FBOs) from feeder-free induced pluripotent stem cells (iPSC)s by regulating a FGF2 concentration and applied this method to generate FBOs from patients with familial AD (fAD FBOs). The obtained fAD FBOs recapitulated the amyloid-β pathology and increased tau phosphorylation but not tau aggregates. To fully induce the tau pathology, FBOs were injected with adeno-associated virus (AAV)-expressing P301L mutant tau. In these Tau-P301L FBOs, tau fibrils were observed in the neuronal cell body and neurites with immunoelectron microscopy, in addition to the sarkosyl-insoluble and thioflavin S-positive phospho-tau aggregates. Collectively, this model can be used as a platform for investigating pathogenetic mechanisms and evaluation of target molecules for drug discovery for tauopathy.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Cell reports methods
- 巻
- 2
- 号
- 9
- 開始ページ
- 100289
- 終了ページ
- 100289
- 出版年月
- 2022年9月19日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1016/j.crmeth.2022.100289
- 共同研究・競争的資金等の研究課題
研究者
下沢 明希
(シモザワ アキ)