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Study of two-step amyloid-beta accumulation in human brains

Research Project

Project/Area Number 18H02725
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionNational Center for Geriatrics and Gerontology

Principal Investigator

Shinohara Mitsuru  国立研究開発法人国立長寿医療研究センター, 分子基盤研究部, 室長 (60800521)

Co-Investigator(Kenkyū-buntansha) 赤津 裕康  名古屋市立大学, 医薬学総合研究院(医学), 教授 (00399734)
菊地 正隆  大阪大学, 医学系研究科, 特任准教授(常勤) (90722538)
齊藤 祐子  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (60344066)
村山 繁雄  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (50183653)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsアルツハイマー病 / 認知症 / アミロイドβ
Outline of Final Research Achievements

By introducing and developing conventional ELISAs as well as ultra-sensitive ELISAs for full-length Aβ and N-terminal truncated Aβ, we have analyzed multiple brain regions of human autopsy brain with different disease stages. In addition to measuring various neuroinflammation markers, we also have measured tau accumulation in each disease stage and each brain region by developing ELISAs that accurately captures tau accumulation, and reported it in an academic journal (Shinohara et al., J Neuropathol & Exp Neurol 2021). Furthermore, comprehensive gene expression analysis was performed to identify genes and pathways that correlate with various Aβ and tau (unpublished data). We are continuing research to verify the involvement of these genes and pathways in Aβ and tau accumulation.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病の原因とされるAβやタウがヒト脳内で蓄積するメカニズムは未だ不明である。一方でそれらの病的蛋白が蓄積する脳領域には特徴があるとともに、Aβ分子種によってその領域的な特徴は異なっており、蓄積を理解するヒントになる。本研究における成果によって、脳内でどのようにそれらの病的蛋白が蓄積するのか分子的な機序を理解する基盤につながると考えられる。引き続き研究を進め、脳内で全長型Aβや断片化Aβがなぜ蓄積し、どのようにタウの蓄積と結びつくのかを明らかにし、治療薬や予防薬の開発に役立てたいと考える。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease2021

    • Author(s)
      Shinohara Mitsuru、Kikuchi Masataka、Onishi‐Takeya Miyuki、Tashiro Yoshitaka、Suzuki Kaoru、Noda Yasuhiro、Takeda Shuko、Mukouzono Masahiro、Nagano Seiichi、Fukumori Akio、Morishita Ryuichi、Nakaya Akihiro、Sato Naoyuki
    • Journal Title

      FASEB BioAdvances

      Volume: - Issue: 5 Pages: 323-333

    • DOI

      10.1096/fba.2020-00151

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interaction between APOE genotype and diabetes in cognitive decline2020

    • Author(s)
      Shinohara Mitsuru、Tashiro Yoshitaka、Suzuki Kaoru、Fukumori Akio、Bu Guojun、Sato Naoyuki
    • Journal Title

      Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

      Volume: 12 Issue: 1 Pages: 2425-2435

    • DOI

      10.1002/dad2.12006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased levels of Aβ42 decrease the lifespan of ob/ob mice with dysregulation of microglia and astrocytes2020

    • Author(s)
      Shinohara Mitsuru、Tashiro Yoshitaka、Shinohara Motoko、Hirokawa Junko、Suzuki Kaoru、Onishi‐Takeya Miyuki、Mukouzono Masahiro、Takeda Shuko、Saito Takashi、Fukumori Akio、Saido Takaomi C.、Morishita Ryuichi、Sato Naoyuki
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 2 Pages: 2425-2435

    • DOI

      10.1096/fj.201901028rr

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 原因因子や危険因子に着目した病態解明, 治療薬開発2020

    • Author(s)
      篠原 充
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] タウELISA の剖検脳での検討2020

    • Author(s)
      篠原 充
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 危険因子にも着目したアルツハイマー病の病態機構の解明、治療薬開発の研究2020

    • Author(s)
      篠原 充
    • Organizer
      第62回日本老年医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] サンドイッチELISAを活用した剖検脳研究からの知見2019

    • Author(s)
      篠原 充
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ob/obマウスにおけるAβ42の増加は寿命を短くさせる2019

    • Author(s)
      篠原 充
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 危険因子にも着目したアルツハイマー病の治療標的の同定と治療薬の開発2019

    • Author(s)
      篠原 充
    • Organizer
      第8回 大阪大学神経難病フォーラム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Increased Levels of Aβ42 Decrease the Lifespan of Ob/Ob Mice with Dysregulation of Microglia and Astrocytes2019

    • Author(s)
      Mitsuru Shinohara
    • Organizer
      Alzheimer's Association International Conference 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Implications from Alzheimer's disease risk factors2019

    • Author(s)
      Mitsuru Shinohara
    • Organizer
      The 5th NCGG-ICAH Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Insights from biochemical analyses of regional distribution of Alzheimer's pathologies2018

    • Author(s)
      篠原 充
    • Organizer
      ICN2018 TOKYO
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] The Roles of Apolipoprotein E, Lipids, and Glucose in the Pathogenesis of Alzheimer's Disease2019

    • Author(s)
      Mitsuru Shinohara, Naoyuki Sato
    • Total Pages
      17
    • Publisher
      Springer, Singapore
    • ISBN
      9789811335396
    • Related Report
      2019 Annual Research Report
  • [Book] Diabetes Mellitus, A risk factor for Alzheimer's Disease2019

    • Author(s)
      Mitsuru Shinohara, Naoyuki Sato
    • Total Pages
      17
    • Publisher
      Springer, Singapore
    • ISBN
      9789811335396
    • Related Report
      2018 Annual Research Report
  • [Remarks] 分子基盤研究部の篠原充室長、里直行部長のグループは糖尿病の認知機能への影響がAPOE遺伝子型で異なる

    • URL

      https://www.ncgg.go.jp/camd/news/20200214.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 分子基盤研究部の篠原充室長、里直行部長らは共同研究にて肥満・糖尿病とアルツハイマー病

    • URL

      https://www.ncgg.go.jp/camd/news/20191225.html

    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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