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Elucidation of the role of glial cell in tau transmission and axonal degeneration in Alzheimer's disease and targeted therapy with glial cell

Research Project

Project/Area Number 17K09757
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKyushu University

Principal Investigator

Asai Hirohide  九州大学, 医学研究院, 共同研究員 (50510210)

Co-Investigator(Kenkyū-buntansha) 山口 浩雄  九州大学, 大学病院, 特任講師 (00701830)
山崎 亮  九州大学, 医学研究院, 准教授 (10467946)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsアルツハイマー病 / アミロイドβタンパク / ミクログリア / エキソソーム / マイクロRNA / リン酸化タウタンパク / バイオマーカー / CD33 / 毒性アミロイドベータ / 病的タウ / タウ蛋白 / グリア炎症 / 神経科学
Outline of Final Research Achievements

Since exosomes cross the blood-brain barrier, we extracted exosomes from the peripheral blood of APP-KI mouse models of Alzheimer's disease (AD) and attempted to detect toxic turn Aβ42 by dot blotting with success. We extracted microRNAs (miRNAs) from these exosomes and compared AD and wild-type mice by next-generation sequencing, and found that only one miRNA was up-regulated and five miRNAs were down-regulated. These potential blood-based biomarkers may lead to earlier diagnosis as well as new targets for AD treatment. Further analyses using human samples are now under way.

Academic Significance and Societal Importance of the Research Achievements

神経細胞以外のアストログリア、オリゴデンドログリア由来のエキソソームも血液中に存在しており、これらのエキソソームの解析によって、軽度認知障害やアルツハイマー病の分子病態の本態が解明される。エキソソームは、血液脳関門を双方向に通過できることから、ドラッグデリバリーとしても利用することかできる。また、同様の細胞特異的エキソソームが腫瘍や免疫疾患などの多くのヒト疾患の分子病態解明につながることへ貢献でき、神経疾患以外においても応用できる可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Insulin deficiency promotes formation of toxic amyloid-beta42 conformer co-aggregating with hyper-phosphorylated tau oligomer in an Alzheimer's disease model.2020

    • Author(s)
      Imamura T, Yanagihara YT, Ohyagi Y, Nakamura N, Iinuma KM, Yamasaki R, Asai H, Maeda M, Murakami K, Ilie K, Kira JI
    • Journal Title

      Neurobiology of Disease

      Volume: 137 Pages: 104739-104739

    • DOI

      10.1016/j.nbd.2020.104739

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Association CD33 expression with toxic turn amyloid βprotein 42 in APP-KI mice2019

    • Author(s)
      Tomohiro Imamura, Hirohide Asai, Ryo Yamasaki, Jun-ichi Kira
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Possible regulatory roles of miRNAs in APP-KI AD model mice2019

    • Author(s)
      Tomohiro Imamura, Hirohide Asai, Ryo Yamasaki, Jun-ichi Kira
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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