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Comprehensive PET imaging for oxidative stress and tau to clarify the pathogenesis of Alzheimer's disease

Research Project

Project/Area Number 20K07900
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionUniversity of Fukui

Principal Investigator

Ikawa Masamichi  福井大学, 学術研究院医学系部門, 講師 (60444212)

Co-Investigator(Kenkyū-buntansha) 岡沢 秀彦  福井大学, 高エネルギー医学研究センター, 教授 (50360813)
米田 誠  福井県立大学, 看護福祉学部, 教授 (70270551)
平山 暁  筑波技術大学, 保健科学部, 教授 (20323298)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsアルツハイマー病 / 酸化ストレス / タウ / PETイメージング / 認知症
Outline of Research at the Start

アルツハイマー病(AD)では,アミロイドβ・タウ蓄積への酸化ストレス(フリーラジカル増加)の関与が想定されている.本研究では,64Cu-ATSM(酸化ストレス)・11C-PiB(アミロイド)・18F-MK-6240(タウ)によるPETと機能的MRI(神経変性)を併せた包括的イメージングおよび血中フリーラジカル測定をAD患者と健常者に実施し,AD病態におけるタウ蓄積に対する酸化ストレスの関与を検証する.本研究によって,酸化ストレスとタウを中心としたAD病態の包括的な可視化という新たな評価法を確立し,タウ病変・病態進展の“加速因子”としての酸化ストレスの影響を解明する.

Outline of Final Research Achievements

In this study, PET/MRI imaging with 64Cu-ATSM for oxidative stress and 11C-PiB for amyloid-β were performed in patients with Alzheimer's disease (AD) and healthy subjects. We found a significant increase in cerebral oxidative stress in the hippocampus and posterior cingulate gyrus in patients with early-stage AD using kinetic analysis of 64Cu-ATSM accumulation. After approval by the Institutional Ethics Review Board, we launched tau PET imaging using 18F-MK6240 to evaluate tau accumulation in the brain. Furthermore, we developed a noninvasive quantitative method to measure 11C-PiB accumulation. In addition, we revealed various neurophysiological changes using multimodal PET/MRI.

Academic Significance and Societal Importance of the Research Achievements

本研究での64Cu-ATSM PET/MRIによる酸化ストレスイメージングによって,アルツハイマー病(AD)患者脳内における酸化ストレスの増加が示され,AD病態への酸化ストレスの関与を明らかにすることができた.本研究によって,酸化ストレスとアミロイドβ・タウ病変,神経生理学的変化を含めたAD病態のPET/MRIイメージングによる包括的な可視化という新たな評価法を確立することができた.本研究の成果から,ADにおけるアミロイドβ・タウ病変や病態の進展に対する“神経変性因子”としての酸化ストレスの役割の解明につながり,さらに酸化ストレスを標的とした新規治療薬の開発に貢献できることが期待される.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2023 2022 2021 2020

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (6 results) (of which Invited: 3 results) Book (2 results)

  • [Journal Article] Regional cortical hypoperfusion and atrophy correlate with striatal dopaminergic loss in Parkinson's disease: a study using arterial spin labeling MR perfusion.2023

    • Author(s)
      Kitazaki Y, Ikawa M, Yamaguchi T, Enomoto S, Shirafuji N, Yamamura O, Tsujikawa T, Okazawa H, Kimura H, Nakamoto Y, Hamano T.
    • Journal Title

      Neuroradiology

      Volume: 65 Issue: 3 Pages: 569-577

    • DOI

      10.1007/s00234-022-03085-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebral Oxidative Stress in Early Alzheimer’s Disease Evaluated by 64Cu-ATSM PET/MRI: A Preliminary Study2022

    • Author(s)
      Okazawa Hidehiko、Ikawa Masamichi、Tsujikawa Tetsuya、Mori Tetsuya、Makino Akira、Kiyono Yasushi、Nakamoto Yasunari、Kosaka Hirotaka、Yoneda Makoto
    • Journal Title

      Antioxidants

      Volume: 11 Issue: 5 Pages: 1022-1022

    • DOI

      10.3390/antiox11051022

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arterial spin labeling imaging for the detection of cerebral blood flow asymmetry in patients with corticobasal syndrome.2022

    • Author(s)
      Yamaguchi T, Ikawa M, Enomoto S, Shirafuji N, Yamamura O, Tsujikawa T, Okazawa H, Kimura H, Nakamoto Y, Hamano T.
    • Journal Title

      Neuroradiology.

      Volume: - Issue: 9 Pages: 1829-1837

    • DOI

      10.1007/s00234-022-02942-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative Evaluation of 18F-Flutemetamol PET in Patients With Cognitive Impairment and Suspected Alzheimer's Disease: A Multicenter Study2021

    • Author(s)
      Matsuda H, Ito K , Ishii K, Shimosegawa E, Okazawa H, Mishina M, Mizumura S, Ishii K, Okita K, Shigemoto Y, Kato T, Takenaka A, Kaida H, Hanaoka K, Matsunaga K, Hatazawa J, Ikawa M, Tsujikawa T, Morooka M, Ishibashi K, Kameyama M, Yamao T, Miwa K, Ogawa M, Sato N.
    • Journal Title

      Frontiers in Neurology

      Volume: 11 Pages: 578753-578753

    • DOI

      10.3389/fneur.2020.578753

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ミトコンドリア脳筋症・乳酸アシドーシス・脳卒中様発作症候群(MELAS)2021

    • Author(s)
      井川 正道、米田 誠
    • Journal Title

      救急医学

      Volume: 45 Pages: 461-467

    • Related Report
      2021 Research-status Report
  • [Journal Article] Molecular imaging for mitochondrial metabolism and oxidative stress in mitochondrial diseases and neurodegenerative disorders2021

    • Author(s)
      Ikawa Masamichi、Okazawa Hidehiko、Yoneda Makoto
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1865 Issue: 3 Pages: 129832-129832

    • DOI

      10.1016/j.bbagen.2020.129832

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PET Imaging for Oxidative Stress in Neurodegenerative Disorders Associated with Mitochondrial Dysfunction2020

    • Author(s)
      Ikawa Masamichi、Okazawa Hidehiko、Nakamoto Yasunari、Yoneda Makoto
    • Journal Title

      Antioxidants

      Volume: 9 Issue: 9 Pages: 861-861

    • DOI

      10.3390/antiox9090861

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noninvasive Measurement of [11C]PiB Distribution Volume Using Integrated PET/MRI2020

    • Author(s)
      Okazawa Hidehiko、Ikawa Masamichi、Tsujikawa Tetsuya、Makino Akira、Mori Tetsuya、Kiyono Yasushi、Kosaka Hirotaka
    • Journal Title

      Diagnostics

      Volume: 10 Issue: 12 Pages: 993-993

    • DOI

      10.3390/diagnostics10120993

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] アルツハイマー病患者における酸化ストレスPETイメージング2023

    • Author(s)
      井川 正道、岡沢 秀彦、辻川 哲也、森 哲也、牧野 顕、清野 泰、中本 安成、小坂 浩隆、米田 誠
    • Organizer
      第21回日本ミトコンドリア学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 診療におけるIRUD-自験例を通して考える2023

    • Author(s)
      井川 正道
    • Organizer
      第61回日本臨床検査医学会 東海・北陸支部総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Regional cortical hypoperfusion and atrophy correlated with dopaminergic loss in Parkinson's disease2022

    • Author(s)
      Ikawa M, Kitazaki Y, Yamaguchi T, Enomoto S, Shirafuji N, Yamamura O, Tsujikawa T, Okazawa H, Kimura H, Nakamoto Y, Hamano T
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] MRI ASLによる大脳皮質基底核症候群での脳血流の左右差の評価2021

    • Author(s)
      山口 智久、井川 正道、白藤 法道、山村 修、木村 浩彦、濱野忠則
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 酸化ストレスのイメージング2020

    • Author(s)
      井川 正道
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 神経変性疾患における酸化ストレス:イメージングによる病態評価2020

    • Author(s)
      井川 正道、岡沢 秀彦、米田 誠
    • Organizer
      第63回日本脳循環代謝学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Book] 今日の治療指針 2023年版[デスク判]2023

    • Author(s)
      井川 正道
    • Total Pages
      1
    • Publisher
      医学書院
    • ISBN
      9784260050357
    • Related Report
      2022 Annual Research Report
  • [Book] 最新主要文献とガイドラインでみる 脳神経内科学レビュー 2022-’232022

    • Author(s)
      井川 正道
    • Total Pages
      6
    • Publisher
      総合医学社
    • ISBN
      4883784649
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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