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Identification of cholesterol efflux pathway which regulates amyloid beta production

Research Project

Project/Area Number 17H07095
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Laboratory medicine
Research InstitutionJuntendo University

Principal Investigator

yano kouji  順天堂大学, 医学(系)研究科(研究院), 博士研究員 (40802955)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsコレステロール / iPS細胞 / アルツハイマー病 / 神経細胞 / カルシウムチャネル / マルチ電極アレイシステム / ABCA1 / アポリポ蛋白 / コレステロール代謝 / カルシウム代謝
Outline of Final Research Achievements

In this study, we succeeded in differentiating Alzheimer's disease patient-derived iPS cells into the forebrain neuron, which is the site of predilection for Alzheimer's disease is, and midbrain regions. We also established a method to increase and decrease the cholesterol content of both neurons, and showed the possibility to be a new tool to show the relationship between Alzheimer's disease and cholesterol metabolism. In addition, it is possible to analyze the expression of transporters involved in cholesterol transport. These results shows the usefulness of iPS cell-derived neurons.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病は認知症患者の中で最も割合が高く、高齢化を迎えた本邦においては今後社会的な問題になることが強く予想される。他方で、アルツハイマー病の有効な治療薬は存在しない。これらの原因として、適切なモデル動物・細胞が存在しないことが挙げられる。ヒトiPS細胞を用いたことでヒト遺伝情報を持った神経細胞による病態解析を行える点において学術的に非常に意義が高い。さらに、食分化の変化とともに脂質異常症は日本でも問題である一方で脂質異常とアルツハイマー病との関連を示した研究は非常に少なく、本研究による検討はこれまでにない視点から解析を行った点において社会的に意義が高い。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (3 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Soluble LR11 competes with amyloid β in binding to cerebrospinal fluid?high-density lipoprotein2019

    • Author(s)
      Yano Kouji、Hirayama Satoshi、Misawa Naomi、Furuta Ayaka、Ueno Tsuyoshi、Motoi Yumiko、Seino Utako、Ebinuma Hiroyuki、Ikeuchi Takeshi、Schneider Wolfgang J.、Bujo Hideaki、Miida Takashi
    • Journal Title

      Clinica Chimica Acta

      Volume: 489 Pages: 29-34

    • DOI

      10.1016/j.cca.2018.11.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Establishment of neuroelectrophysiological model for Alzheimer disease derived from human iPSCs2018

    • Author(s)
      Yano K, Ai T, Shiga T, Akamatsu W, Hirayama S, Miida T
    • Organizer
      第50回 日本動脈硬化学会 総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Loading of Ca2+ indicator in the human iPSC-derived neurons with PSN1/2 mutations.2017

    • Author(s)
      矢野康次
    • Organizer
      第49回 日本動脈硬化学会 総会 学術集会 広島
    • Related Report
      2017 Annual Research Report

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Published: 2017-08-25   Modified: 2020-03-30  

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