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Brain-derived exosomes in plasma as a potential biomarker for Parkinson's and related diseases

Research Project

Project/Area Number 20K16605
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Ohmichi Takuma  京都府立医科大学, 医学(系)研究科(研究院), 助教 (60869288)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsパーキンソン病 / 血液バイオマーカー / LRG / zonulin / 腸管炎症 / ロイシンリッチα2グリコプロテイン / ゾヌリン / ホスホグリセリン酸キナーゼ / カフェイン / 多系統萎縮症 / 脳細胞由来エクソソーム / エクソソーム / 進行性核上性麻痺
Outline of Research at the Start

本研究の概要は、ヒト血液中にある脳細胞由来のエクソソーム(細胞内分子を細胞間の運搬や細胞外への排出を担う40-100nmの微小小胞)を定量化する方法を確立し、実際のヒト血液検体を用いて、脳細胞由来エクソソーム量やエクソソーム内に含まれる特異的な蛋白を測定することで、臨床症状が出現する前からパーキンソン病、多系統萎縮症、進行性核上性麻痺を診断できる血液バイオマーカーを確立する研究である。さらに、脳細胞由来エクソソームを血漿から分離する測定方法を確立し、エクソソーム量が多施設で測定できるように標準化することで日常臨床で使用できるにすることを目標とする。

Outline of Final Research Achievements

Our study aimed to establish a quantification system for brain-derived exosomes in human plasma. We collected peripheral blood plasma from patients with PD and disease controls. However, we were unable to complete the separation and extraction of exosomes from the collected samples. Therefore, we focused on measuring disease-specific proteins in the plasma of PD and PS patients and identified potential blood biomarkers. One candidate, Leucine-rich α2 glycoprotein (LRG), was highlighted. LRG is known to increase in conditions such as rheumatoid arthritis and inflammatory bowel diseases. We confirmed elevated serum LRG levels in PD patients. Additionally, we investigated Zonulin as a candidate biomarker for intestinal inflammation in PD. Although we measured serum Zonulin levels in PD patients, there was no correlation with clinical parameters or serum cytokine levels. These results suggest that serum LRG levels may reflect intestinal inflammation in PD.

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病は、病理学的にも症候学的にも多様性を持った疾患である。本研究におけるパーキンソン病の腸管炎症のバイオマーカーの開発によって、パーキンソン病における腸管炎症の病態解明と疾患の早期診断が可能となることが期待される。また、多様であるパーキンソン病のバイオマーカーによる分類によって、個別化医療を推進することも期待できる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (11 results)

All 2024 2023 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (6 results)

  • [Journal Article] Serum leucine-rich α2 glycoprotein as a potential biomarker for systemic inflammation in Parkinson’s disease2023

    • Author(s)
      Ohmichi Takuma、Kasai Takashi、Shinomoto Makiko、Kitani-Morii Fukiko、Fujino Yuzo、Menjo Kanako、Mizuno Toshiki
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 2 Pages: e0282153-e0282153

    • DOI

      10.1371/journal.pone.0282153

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impaired age-dependent increases in phosphoglycerate kinase activity in red blood cells of Parkinson's disease patients2021

    • Author(s)
      Fujino Yuzo、Kasai Takashi、Kitani-Morii Fukiko、Ohmichi Takuma、Shinomoto Makiko、Menjo Kanako、Mizuno Toshiki
    • Journal Title

      Parkinsonism & Related Disorders

      Volume: 91 Pages: 128-134

    • DOI

      10.1016/j.parkreldis.2021.09.016

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebral spinal fluid biomarker profiles in CNS infection associated with HSV and VZV mimic patterns in Alzheimer’s disease2021

    • Author(s)
      Shinomoto Makiko、Kasai Takashi、Tatebe Harutsugu、Kitani-Morii Fukiko、Ohmichi Takuma、Fujino Yuzo、Allsop David、Mizuno Toshiki、Tokuda Takahiko
    • Journal Title

      Translational Neurodegeneration

      Volume: 10 Issue: 1 Pages: 2-2

    • DOI

      10.1186/s40035-020-00227-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Risk factors for neuropsychiatric symptoms in patients with Parkinson’s disease during COVID-19 pandemic in Japan2021

    • Author(s)
      Kitani-Morii Fukiko、Kasai Takashi、Horiguchi Go、Teramukai Satoshi、Ohmichi Takuma、Shinomoto Makiko、Fujino Yuzo、Mizuno Toshiki
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 1 Pages: 0245864-0245864

    • DOI

      10.1371/journal.pone.0245864

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of Blood Caffeine Levels in Patients With Parkinson's Disease and Multiple System Atrophy by Caffeine ELISA2020

    • Author(s)
      Ohmichi Takuma、Kasai Takashi、Shinomoto Makiko、Matsuura Jun、Koizumi Takashi、Kitani-Morii Fukiko、Tatebe Harutsugu、Sasaki Hidenao、Mizuno Toshiki、Tokuda Takahiko
    • Journal Title

      Frontiers in Neurology

      Volume: 11 Pages: 580127-580127

    • DOI

      10.3389/fneur.2020.580127

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Serum leucine-rich a2 glycoprotein levels correlate with bowel inflammation in Parkinson's disease2024

    • Author(s)
      大道卓摩, 笠井高士, 森井芙貴子, 藤野雄三, 篠本真紀子, 毛受奏子, 水野敏樹
    • Organizer
      第65回日本神経学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] パーキンソン病の全身性炎症マーカーとしての 血清Leucine-rich α2 glycoprotein濃度の有用性の検討2023

    • Author(s)
      大道卓摩, 笠井高士, 篠本真紀子, 森井芙貴子, 藤野雄三, 毛受奏子, 水野敏樹
    • Organizer
      第17回日本パーキンソン病・運動障害疾患コングレス
    • Related Report
      2023 Annual Research Report
  • [Presentation] Serum zonulin levels in patients with Parkinson’s disease2023

    • Author(s)
      大道卓摩, 篠本真紀子, 芦田真士, 笠井高士, 森井芙貴子, 藤野雄三, 毛受奏子,水野敏樹
    • Organizer
      第64回日本神経学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Leucine-rich α2 glycoprotein as a possible biomarker for the inflammation of Parkinson's disease2022

    • Author(s)
      大道卓摩, 笠井高士, 篠本真紀子, 森井芙貴子, 藤野雄三, 毛受奏子, 水野敏樹
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Proposal for serum theophylline as an alternative biomarker to caffeine in PD diagnosis2021

    • Author(s)
      Takuma Ohmichi, Takashi Kasai, Makiko Shinomoto, Fukiko Kitani-morii, Harutsugu Tatebe, Yuzo Fujino, Toshiki Mizuno, Takahiko Tokuda
    • Organizer
      日本神経学会
    • Related Report
      2021 Research-status Report
  • [Presentation] パーキンソン病と多系統萎縮症の患者のカフェイン値の定量(Quantification of caffeine levels in patients with Parkinson's disease and multiple system atrophy)2020

    • Author(s)
      Ohmichi Takuma , Kasai Takashi , Tatebe Harutsugu , Kitani-Morii Fukiko , Shinomoto Makiko , Mizuno Toshiki , Tokuda Takahiko
    • Organizer
      (一社)日本神経学会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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