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Significance and clinical application of GDF15 in mitochondrial dysfunction in Alzheimer's disease

Research Project

Project/Area Number 17K15887
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionUniversity of Tsukuba

Principal Investigator

Tsuji Hiroshi  筑波大学, 医学医療系, 講師 (40633970)

Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsGDF15 / GDF-15 / リンパ腫 / 多発性硬化症 / Tumafactive lesion / PGRN / ミトコンドリア / アルツハイマー病 / 神経変性疾患 / パーキンソン病 / 認知症
Outline of Final Research Achievements

A secreted protein called GDF15 (Growth/differentiation factor 15) reflects mitochondrial function. Elucidating the dynamics of GDF15 in biological samples may clarify AD and mitochondrial dysfunction. We, therefore, measured and compared GDF15 levels in cerebrospinal fluid in multiple sclerosis (MS), central nervous system lymphoma (CNS lymphoma), and glioma. The cerebrospinal fluid GDF15 values of 9 patients with multiple sclerosis, 6 patients with CNS lymphoma, and 3 patients with glioblastoma were 320.4±246.5 pg/ml, 419.5±237.6 pg/ml, and 471.0±237.6 pg/ml, respectively. The values were significantly higher in CNS lymphoma and glioma compared with MS (P = 0.009, P = 0.037). Based on the above results, GDF15 is useful in distinguishing between MS and malignant diseases of the central nervous system. These results show that GDF15 can be measured in clinical samples and used for neurodegenerative diseases such as Alzheimer’s disease.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー型認知症は,高齢化社会と共に罹患者数が増加傾向にあり,社会問題となっている.アルツハイマー病の原因にアミロイドβ蛋白が,疾患感受性遺伝子にアポリポ蛋白Eのアイソフォームが関わってくる.これらの蛋白は神経細胞内の酸化ストレスに影響され,その細胞内の酸化を担うのがミトコンドリアである.最近,ミトコンドリア機能異常がアルツハイマー病の発症と関係があることが報告されており,またミトコンドリア機能を反映するのが,GDF15という分泌性蛋白である.本研究ではGDF15を髄液で測定できることが明らかとなり、臨床応用が可能となった。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (10 results)

All 2022 2020 2019 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Superficial siderosis of the central nervous system despite successful treatment of cerebral arteriovenous malformation: A case report2020

    • Author(s)
      Tsuji Hiroshi、Ouchi Shogo、Okune Sho、Yamazaki Daichi、Hayakawa Mikito、Sato Masayuki、Masuda Yosuke、Hosaka Ai、Tamaoka Akira
    • Journal Title

      Interdisciplinary Neurosurgery

      Volume: 20 Pages: 100671-100671

    • DOI

      10.1016/j.inat.2020.100671

    • NAID

      120007159559

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pembrolizumab treatment of metastatic urothelial cancer without exacerbating myasthenia gravis2020

    • Author(s)
      Ishii Akiko、Yokoyama Minato、Tsuji Hiroshi、Fujii Yasuhisa、Tamaoka Akira
    • Journal Title

      eNeurologicalSci

      Volume: 19 Pages: 100236-100236

    • DOI

      10.1016/j.ensci.2020.100236

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GDF-15, a mitochondrial disease biomarker, is associated with the severity of multiple sclerosis2019

    • Author(s)
      Nohara S, Ishii A, Yamamoto F, Yanagiha K, Moriyama T, Tozaka N, Miyake Z, Yatsuga S, Koga Y, Hosaka T, Terada M, Yamaguchi T, Aizawa S, Mamada N, Tsuji H, Tomidokoro Y, Nakamagoe K, Ishii K, Watanabe M, Tamaoka A
    • Journal Title

      Journal of the neurological sciences

      Volume: 405 Pages: 116429-116429

    • DOI

      10.1016/j.jns.2019.116429

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alien leg phenomenon in corticobasal syndrome2019

    • Author(s)
      Nohara Seitaro、Tsuji Hiroshi、Tamaoka Akira
    • Journal Title

      Journal of Clinical Neuroscience

      Volume: 64 Pages: 254-255

    • DOI

      10.1016/j.jocn.2019.03.053

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Meningeal carcinomatosis presenting with leukoencephalopathy-like imaging findings2019

    • Author(s)
      Tsuji Hiroshi、Ayako Shioya、Takayashiki Norio、Irie Toshiyuki、Itoi Satoshi、Kodama Taisuke、Kaji Yuki、Matsuoka Ryota、Mashiko Ryota、Shibata Yasushi、Ishii Akiko、Siato Yuko、Tamaoka Akira
    • Journal Title

      eNeurologicalSci

      Volume: 14 Pages: 21-23

    • DOI

      10.1016/j.ensci.2018.11.018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lateral medullary infarction in a patient with central nervous system lupus.2017

    • Author(s)
      Kato M1, Chino Y2, Sato R1, Kinoshita K1, Tsuji H3, Tokuda Y4, Tamaoka A5, Sumida T6.
    • Journal Title

      Int J Rheum Dis.

      Volume: 20 Issue: 11 Pages: 1808-1811

    • DOI

      10.1111/1756-185x.12610

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 多発性硬化症と腫瘍性疾患の鑑別におけるGDF-15の有用性の検討2022

    • Author(s)
      辻 浩史, 冨所 康志, 中馬越 清隆, 石井 亜紀子, 石井 一弘, 小川 靖裕, 玉岡 晃
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 多発性硬化症と中枢神経腫瘍性疾患の鑑別における髄液中プログラニューリン の検討2020

    • Author(s)
      辻 浩史
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 辺縁系脳炎におけるGDF15およびFGF21の検討2017

    • Author(s)
      石井 亜紀子(筑波大学附属病院 神経内科), 山本 詞子, 野原 誠太郎, 柳葉 久実, 森山 哲也, 遠坂 直希, 三宅 善嗣, 八ツ賀 秀一, 古賀 靖敏, 保坂 孝史, 寺田 真, 山口 哲人, 相澤 哲史, 儘田 直美, 辻 浩史, 冨所 康志, 中馬越 清隆, 石井 一弘, 渡邊 雅彦, 玉岡 晃
    • Organizer
      WCN2017: XXIII World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多発性硬化症/視神経脊髄炎におけるGDF-15、FGF-21の検討2017

    • Author(s)
      野原 誠太郎(筑波大学 医学医療系神経内科), 石井 亜紀子, 山本 詞子, 遠坂 直希, 三宅 善嗣, 森山 哲也, 柳葉 久実, 保坂 孝史, 寺田 真, 山口 哲人, 儘田 直美, 辻 浩史, 冨所 康志, 中馬越 清隆, 石井 一弘, 渡邊 雅彦, 八ツ賀 秀一, 古賀 靖敏, 玉岡 晃
    • Organizer
      WCN2017: XXIII World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2024-01-30  

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