The role of microglia in the propagation of tau aggregates

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07825
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kagoshima University
• Principal Investigator: Matsumoto Shin-Ei 鹿児島大学, 医歯学域医学系, 助教 (40432950)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: タウオパチー / ミクログリア / TREM2 / タウ

Outline of Final Research Achievements

It has been shown that tau aggregation and propagation are closely related to the progression of tauopathies including Alzheimer's disease (AD). It has also been reported that the C-terminal fragment (CTF) of tau, which contains the microtubule-binding domain, is more easily aggregated than full-length tau. On the other hand, it has been suggested that microglia may be involved in tau propagation via TREM2, a risk factor for AD.
In this study, we attempted to generate transgenic mice expressing Tau-CTF as a new tauopathy model mouse by genome editing and analyze them. In addition, to elucidate the role of TREM2 in the tau propagation model, we generated TREM2-deficient and TREM2 R47H knock-in mice by genome editing and analyzed them.

Free Research Field

病態神経科学、免疫学

Academic Significance and Societal Importance of the Research Achievements

タウオパチーにおける凝集タウの伝播のメカニズムはほとんど不明でありTREM2およびミクログリアの関与についても不明な点が多い。本研究で確立したTREM2ノックアウトマウスおよびTREM2 R47Hノックインマウスは、タウオパチーの病態におけるTREM2の役割の解明に非常に有用であると考えられる。一方、最近の報告では神経変性疾患だけではなく肥満やがんなど他の疾患においてもTREM2が重要な役割を果たしている可能性が示されており、本研究結果はタウオパチーのみならずTREM2が関与する様々な疾患の機序解明および治療法の開発に寄与すると考えられる。