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PET study of brain tau deposition in traumatic brain injury using [11C]PBB3

Research Project

Project/Area Number 16K19789
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Psychiatric science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Takahata Keisuke  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, 研究員(任常) (20645311)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords頭部外傷 / 慢性外傷性脳症 / CTE / タウPET / タウオパチー / 脳しんとう / 頭部外傷後精神病 / ボクサー脳症 / 神経科学 / 精神医学 / タウ / ポジトロン断層法
Outline of Final Research Achievements

In the present study, we assessed fibrillary tau deposits in the brains of long-term survivors of TBI versus age-matched HC subjects using PET with [11C]PBB3. TBI patients showed increased [11C]PBB3 binding capacity in widespread brain regions compared to age-matched HC subjects. TBI patients with traumatic encephalopathy syndrome (TES) showed a higher [11C]PBB3 binding capacity in the WM segment than those without TES, especially in the frontal WM segment. Additional analysis showed that higher [11C]PBB3 binding capacity values were mainly due to increased radiosignals in the surface white matter. Interestingly, such a distribution of the tau tracer in the present study is unique to TBI, and distinct from that of AD. Moreover, [11C]PBB3 binding capacity in the WM segment was positively correlated with the severity of psychosis. These findings suggest a close link between tau neuropathology and late-onset neuropsychiatric symptoms following TBI.

Academic Significance and Societal Importance of the Research Achievements

本研究は、頭部外傷によって引き起こされる慢性外傷性脳症(CTE)などの遅発性症候の症候が引き起こされる機序を初めて明らかにしただけでなく、頭部外傷によるタウ病変のイメージングバイオマーカーとしてタウPETが有用であることを示した。これらの成果は、(1)将来的に実用化が期待されるタウに対する免疫抗体療法の治療効果判定法や新薬開発の評価指標としての活用や、(2)CTEの早期介入や治療導入を判定するための早期診断法としての活用に貢献することが期待される。また、コンタクトスポーツにおける頭部保護の重要性を広く認識させる上でも重要な成果である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Tau-induced focal neurotoxicity and network disruption related to apathy in Alzheimer’s disease2018

    • Author(s)
      Kitamura Soichiro、Shimada Hitoshi、Niwa Fumitoshi、Endo Hironobu、Shinotoh Hitoshi、Takahata Keisuke、Kubota Manabu、Takado Yuhei、Hirano Shigeki、Kimura Yasuyuki、Zhang Ming-Rong、Kuwabara Satoshi、Suhara Tetsuya、Higuchi Makoto
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 89 Issue: 11 Pages: 1208-1214

    • DOI

      10.1136/jnnp-2018-317970

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuromolecular basis of faded perception associated with unreality experience2018

    • Author(s)
      Yokokawa Keita、Ito Takehito、Takahata Keisuke、Takano Harumasa、Kimura Yasuyuki、Ichise Masanori、Ikoma Yoko、Isato Ayako、Zhang Ming-Rong、Kawamura Kazunori、Ito Hiroshi、Takahashi Hidehiko、Suhara Tetsuya、Yamada Makiko
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 8062-8062

    • DOI

      10.1038/s41598-018-26382-9

    • NAID

      120006551755

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A human PET study of [11C]HMS011, a potential radioligand for AMPA receptors2018

    • Author(s)
      Keisuke Takahata et al.,
    • Journal Title

      EJNMMI research

      Volume: 16 Issue: 1 Pages: 63-63

    • DOI

      10.1186/s13550-017-0313-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Late-onset Neurodegenerative Diseases Following Traumatic Brain Injury: Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease Secondary to TBI (AD-TBI)2016

    • Author(s)
      高畑圭輔、田渕肇、三村將
    • Journal Title

      BRAIN and NERVE

      Volume: 68 Issue: 7 Pages: 849-857

    • DOI

      10.11477/mf.1416200517

    • ISSN
      1344-8129, 1881-6096
    • Year and Date
      2016-07-01
    • Related Report
      2016 Research-status Report
  • [Presentation] Late-life neurodegenerative disorders due to traumatic brain injury: Epidemiology, clinical symptoms and in vivo quantification of neuropathology2018

    • Author(s)
      Keisuke Takahata, Masaru Mimura
    • Organizer
      3rd Japan-US Technical Information Exchange Forum on BLAST INJURY (JUFBI 2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Late-life psychosis ant tau neuropathology: Epidemiology, clinical symptoms and in vivo quantification of neuropathology2018

    • Author(s)
      Keisuke Takahata
    • Organizer
      International Consortium on Hallucination Research (ICHR2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Association between tau neuropathology in TBI patients and late-onset psychiatric symptoms: A PET study2018

    • Author(s)
      Keisuke Takahata et al.,
    • Organizer
      12nd International Symposium of Functional Neuroreceptor Mapping of the Living Brain (NRM2018),
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ニューロイメージングバイオマーカーを用いた創薬とプレシジョン・メティシンの現況2018

    • Author(s)
      高畑 圭輔, 堀口 隆司, 島田 斉, 樋口 真人, 須原 哲也
    • Organizer
      第28回日本臨床精神神経薬理学会 第48回日本神経精神薬理学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Delayed-Onset Psychosis following TBI is Asso- ciated with Tau Depositions in the Neocortex but Not with β-Amyloid Depositions: A Pet Study with [11C] PBB3 and [11C]PiB2017

    • Author(s)
      Keisuke Takahata et al.
    • Organizer
      Society of Biological Psychiatry 2017 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] タウ・アミロイドPETを用いた老年期精神障害の背景病理に関する検討2016

    • Author(s)
      高畑圭輔、森口翔、須原哲也
    • Organizer
      第112回 日本精神神経学会 学術総会
    • Place of Presentation
      千葉
    • Year and Date
      2016-06-02
    • Related Report
      2016 Research-status Report
  • [Book] 頭部外傷と高次脳機能障害2017

    • Author(s)
      高畑圭輔 他
    • Total Pages
      264
    • Publisher
      新興医学出版社
    • ISBN
      9784880028682
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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