In vivo imaging of propagation of tau pathology in chronic traumatic encephalopathy
Project/Area Number |
20K07935
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52030:Psychiatry-related
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Research Institution | National Institutes for Quantum 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, 量子医科学研究所 脳機能イメージング研究部, 研究員 (20645311)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | 慢性外傷性脳症 / タウオパチー / PET / 頭部外傷 / GFAP / 遅発性脳障害 / タウPET / 頭部外傷後遺症 / 血液バイオマーカー / 死後脳 / ボクサー脳症 / 内因性カンナビノイド系 / モノアシルグリセロールリパーゼ / 神経炎症 / タウ / 認知症 |
Outline of Research at the Start |
慢性外傷性脳症における脳内タウ病変を単一症例ごとに評価可能な技術はこれまで存在しなかった。量研機構が開発した [18F]PM-PBB3は、3リピート、4リピート、3+4リピート型の幅広いタウオパチーを検出することが可能な唯一のタウPET薬剤である。本研究は、反復性軽度頭部外傷患者および健常者を対象として、次世代タウPET薬剤[18F]PM-PBB3を用いたPET検査を複数回行う縦断研究である。他にマルチモーダルMRI検査、神経心理検査、頭部打撃に関する指標の収集も行い、タウ蓄積量との関連を検討する。患者リクルートは、申請者が開設している慶應義塾大学病院の専門外来にて行う。
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Outline of Final Research Achievements |
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder associated with mild-repetitive traumatic brain injury. In this study, we performed PET scans with 11C-PiB and 18F-florzolotau, structual MRI, and blood biomarker measurements on 51 TBI patients (mean age 44.8 years, 36 with repetitive mild TBI and 13 with single severe TBI) and 27 healthy subjects (mean age 45.6 years). The repetitive mild TBI (professional boxer) group showed a significant increase in 18F-florzolotau compared to the healthy group in areas such as bilateral frontal lobes. 18F-florzolotau SUVR values in the gray matter positively correlated with cumulative brain damage and plama GFAP levels. We also assessed binding properties of 18F-florzolotau on CTE tau aggregates using human brain samples provided by Boston University.
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Academic Significance and Societal Importance of the Research Achievements |
TBIによって生じるさまざまな晩期後遺症の中でも反復性軽度頭部外傷によって引き起こされる慢性外傷性脳症(CTE)は、国内外で大きな問題となっているが、これまで早期診断法は存在しなかった。本研究は、18F-florzolotau を用いたPETがTBIによって引き起こされる脳内タウ蓄積を高精度に検出することを示し、慢性外傷性脳症の早期診断法の確立に大きく資する研究成果が得られ、予防や新規治療法の開発への応用が期待される。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Impact of Amyloid and Tau PET on Changes in Diagnosis and Patient Management2023
Author(s)
Shimohama S, Tezuka T, Keisuke T, Bun S, Tabuchi H, Seki M, Momota Y, Suzuki N, Morimoto A, Iwabuchi Y, Kubota M, Yamamoto Y, Sano Y, Shikimoto R, Funaki K, Mimura Y, Nishimoto Y, Ueda R, Jinzaki M, Nakahara J, Mimura M, Ito D
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Journal Title
Neurology
Volume: 100
Issue: 3
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Findings of (18) F-PI-2620 tau PET imaging in patients with Alzheimer's disease and healthy controls in relation to the plasma P-tau181 levels in a Japanese sample2022
Author(s)
Bun S, Moriguchi S, Tezuka T, Sato Y, Takahata K, Seki M, Nakajima S, Yamamoto Y, Sano Y, Suzuki N, Morimoto A, Ueda R, Tabuchi H, Ito D, Mimura M.
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Journal Title
Neuropsychopharmacology Reports
Volume: 42
Issue: 4
Pages: 437-448
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] PET-based classification of corticobasal syndrome.2022
Author(s)
Nakano Y, Shimada H, Shinotoh H, Hirano S, Tagai K, Sano Y, Yamamoto Y, Endo H, Matsuoka K, Takahata K, Kubota M, Takado Y, Kimura Y, Ichise M, Ono M, Sahara N, Kawamura K, Zhang MR, Kuwabara S, Suhara T, Higuchi M.
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Journal Title
Parkinsonism & related disorders
Volume: 98
Pages: 92-98
DOI
Related Report
Peer Reviewed
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[Journal Article] First-in-human in vivo imaging and quantification of monoacylglycerol lipase in the brain: a PET study with 18 F-T-4012022
Author(s)
Takahata K, Seki C, Kimura Y, Kubota M, Ichise M, Sano Y, Yamamoto Y, Tagai K, Shimada H, Kitamura S, Matsuoka K, Endo H, Shinotoh H, Kawamura K, Zhang MR, Takado Y, Higuchi M
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Journal Title
Eur J Nucl Med Mol Imaging
Volume: Online ahead of print.
Issue: 9
Pages: 3150-3161
DOI
Related Report
Peer Reviewed
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[Journal Article] A first-in-human study of 11C-MTP38, a novel PET ligand for phosphodiesterase 72021
Author(s)
Kubota Manabu、Seki Chie、Kimura Yasuyuki、Takahata Keisuke、Shimada Hitoshi、Takado Yuhei、Matsuoka Kiwamu、Tagai Kenji、Sano Yasunori、Yamamoto Yasuharu、Okada Maki、Kikuchi Tatsuya、Ichise Masanori、Kawamura Kazunori、Zhang Ming-Rong、Higuchi Makoto
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Journal Title
European Journal of Nuclear Medicine and Molecular Imaging
Volume: 41
Issue: 11
Pages: 2928-2943
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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