In vivo visualization of tau deposits using [18F] THK5351 PET in neurodegenerative tauopathies

• Project/Area Number: 17K09789
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: Kikuchi Akio 東北大学, 医学系研究科, 大学院非常勤講師 (80463785)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: タウオパチー / 大脳皮質基底核症候群 / 進行性核上性麻痺 / アルツハイマー病 / [18F]THK5351 / PET / タウ蛋白凝集体 / モノアミン酸化酵素B / タウ凝集体 / 脳神経疾患 / 臨床 / 神経機能画像

Outline of Final Research Achievements

The pathology of tauopathy is characterized by abnormal accumulation of tau protein and gliosis with increased monoamine oxidase B. We evaluated in vivo visualization of tauopathies using [18F]THK5351 PET, and found increased accumulation of [18F]THK5351 in disease-related lesions in corticobasal syndrome (CBS), progressive supranuclear palsy, and Alzheimer’s disease. [18F]THK5351 accumulation in the middle frontal and inferior temporal gyri were useful in differentiating these diseases. The annual increase of [18F]THK5351 in the patients with CBS was approximately 6.5% in the superior parietal gyrus. [18F]THK5351 PET may be useful in the differential diagnosis of tauopathies and in monitoring the progression of cortical lesions in CBS.

Academic Significance and Societal Importance of the Research Achievements

大脳皮質基底核症候群 (CBS）や進行性核上性麻痺（PSP）などのタウオパチーではタウ蛋白蓄積とそれに引き続き起こるモノアミン酸化酵素B増加を伴うグリオーシスが神経変性や脳機能障害に深く関与するが、CBSの皮質症状やPSPのパーキンソニズムが顕在化した段階では、すでにこの蛋白の脳内蓄積が高度に進展し細胞死を引き起こしていることが予想される。このタウ蛋白凝集体の脳内蓄積をPETによってできるだけ早期発見することができ、タウ蛋白凝集体の脳内排除をめざした新たな治療薬が開発されれば、CBSやPSPの発症予防や進行抑制ができるようになる可能性がある。

Research Products

• [Journal Article] High prevalence of serum anti-NH2-terminal of α-enolase antibodies in patients with multiple system atrophy and corticobasal syndrome (2021)
  • Author(s): Kikuchi A, Yoneda M, Hasegawa T, Matsunaga A, Ikawa M, Nakamura T, Ezura M, Baba T, Sugeno N, Ishiyama S, Nakamoto Y, Takeda A, Aoki M
  • Journal Title: J Neurol Volume: 268 Issue: 11 Pages: 4291-4295
  • DOI: 10.1007/s00415-021-10553-2
  • Peer Reviewed
• [Journal Article] Case Report: Guitarist’s cramp as the initial manifestation of dopa-responsive dystonia with a novel heterozygous GCH1 mutation (2021)
  • Author(s): Hasegawa T, Hosaka T, Harada R, Kawahata I, Hoshino K, Sugeno N, Kikuchi A, Aoki M
  • Journal Title: F1000 Research Volume: 10 Pages: 361-361
  • DOI: 10.12688/f1000research.51433.1
  • Peer Reviewed / Open Access
• [Journal Article] 18F-THK5351 PET imaging in neurodegenerative tauopathies (2021)
  • Author(s): Ezura M, Kikuchi A, Okamura N, Ishiki A, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Baba T, Sugeno N, Yoshida S, Kobayashi J, Kobayashi M, Tano O, Ishiyama S, Nakamura T, Nakashima I, Mugikura S, Iwata R, Taki Y, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
  • Journal Title: Front Aging Neurosci Volume: 13 Pages: 761010-761010
  • DOI: 10.3389/fnagi.2021.761010
  • Peer Reviewed / Open Access
• [Journal Article] 18F-SMBT-1: A Selective and Reversible PET Tracer for Monoamine Oxidase-B Imaging (2020)
  • Author(s): Harada Ryuichi、Hayakawa Yoshimi、Ezura Michinori、Lerdsirisuk Pradith、Du Yiqing、Ishikawa Yoichi、Iwata Ren、Shidahara Miho、Ishiki Aiko、Kikuchi Akio、Arai Hiroyuki、Kudo Yukitsuka、Yanai Kazuhiko、Furumoto Shozo、Okamura Nobuyuki
  • Journal Title: Journal of Nuclear Medicine Volume: 62 Issue: 2 Pages: 253-258
  • DOI: 10.2967/jnumed.120.244400
  • Peer Reviewed
• [Journal Article] Logopenic aphasia due to Lewy body disease dramatically improved with donepezil (2020)
  • Author(s): Kakinuma K, Baba T, Ezura M, Endo K, Saito Y, Narita W, Iizuka O, Yoshiyuki Nishio Y, Kikuchi A, Hasegawa T, Aoki M, Suzuki K
  • Journal Title: eNeurologicalSc Volume: 19 Pages: 100241-100241
  • DOI: 10.1016/j.ensci.2020.100241
  • Peer Reviewed / Open Access
• [Journal Article] Clinical and metabolic changes in Parkinson's disease with atrophy in the nucleus basalis of Meynert (2020)
  • Author(s): Gang M, Baba T, Hosokai Y, Nishio Y, Kikuchi A, Hirayama K, Hasegawa T, Aoki M, Takeda A, Mori E, Suzuki K
  • Journal Title: Mov Disord Volume: in press Issue: 5 Pages: 825-832
  • DOI: 10.1002/mds.27988
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal changes in 18F-THK5351 PET in corticobasal syndrome (2019)
  • Author(s): Ezura M, Kikuchi A, Ishiki A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Baba T, Sugeno N, Oshima R, Yoshida S, Kobayashi J, Kobayashi M, Tano O, Nakashima I, Mugikura S, Iwata R, Taki Y, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
  • Journal Title: Eur J Neurol Volume: 26 Issue: 9 Pages: 1205-1211
  • DOI: 10.1111/ene.13966
  • Peer Reviewed / Open Access
• [Journal Article] Unveiling the coupling of flotillin-1 and extracellular α-synuclein: relevance to dopamine transporter trafficking and Lewy body formation (2019)
  • Author(s): Kobayashi J, Hasegawa T, Sugeno N, Yoshida S, Miki Y, Fukuda M, Kawahata I, Yamakuni T, Tomiyama A, Kawata Y, Ezura M, Kikuchi A, Baba T, Wakabayashi K, Takeda A, Aoki M
  • Journal Title: FASEB Journal Volume: 33 Issue: 9 Pages: 10240-10256
  • DOI: 10.1096/fj.201802051r
  • Peer Reviewed
• [Journal Article] Mutation analysis of LRP10 in Japanese patients with familial Parkinson’s disease, progressive supranuclear palsy, and fronto-temporal dementia (2019)
  • Author(s): Daida K, Nishioka K, Li Y, Yoshino H, Kikuchi A, Hasegawa T, Funayama M, Hattori N
  • Journal Title: Neurobiol Aging Volume: 84 Pages: 235.e11-235.e16
  • DOI: 10.1016/j.neurobiolaging.2019.08.030
  • Peer Reviewed
• [Journal Article] Tau PET imaging: current status and future direction (2018)
  • Author(s): Okamura N, Harada R, Ishiki A, Kikuchi A, Nakamura T, Kudo Y
  • Journal Title: Clin Transl Imaging Volume: 6 Issue: 4 Pages: 305-316
  • DOI: 10.1007/s40336-018-0290-y
  • Peer Reviewed / Open Access
• [Journal Article] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking. (2018)
  • Author(s): Yoshida S, Hasegawa T, Suzuki M, Sugeno N, Kobayashi J, Ueyama M, Fukuda M, Ido-Fujibayashi A, Sekiguchi K, Ezura M, Kikuchi A, Baba T, Takeda A, Mochizuki H, Nagai Y and Aoki M.
  • Journal Title: Hum Mol Genet. Volume: 27 Issue: 5 Pages: 823-836
  • DOI: 10.1093/hmg/ddy003
  • Peer Reviewed / Open Access
• [Journal Article] Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation. (2018)
  • Author(s): Narumi K, Mishima E, Akiyama Y, Matsuhashi T, Nakamichi T, Kisu K, Nishiyama S, Ikenouchi H, Kikuchi A, Izumi R, Miyazaki M, Abe T, Sato H, Ito S
  • Journal Title: Nephron Volume: 138 Issue: 3 Pages: 243-248
  • DOI: 10.1159/000485109
  • Peer Reviewed
• [Journal Article] Longitudinal study of cognitive and cerebral metabolic changes in Parkinson's disease. (2017)
  • Author(s): Baba T, Hosokai Y, Nishio Y, Kikuchi A, Hirayama K, Suzuki K, Hasegawa T, Aoki M, Takeda A, Mori E.
  • Journal Title: J Neurol Sci Volume: 372 Pages: 288-293
  • DOI: 10.1016/j.jns.2016.11.068
  • Peer Reviewed
• [Journal Article] Membrane Trafficking Illuminates a Path to Parkinson’s Disease (2017)
  • Author(s): Hasegawa T, Sugeno N, Kikuchi A, Baba T, Aoki M.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 242 Issue: 1 Pages: 63-76
  • DOI: 10.1620/tjem.242.63
  • NAID: 130005679072
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Presentation] アストログリオーシスのイメージング (2020)
  • Author(s): 菊池昭夫
  • Organizer: 第61回日本神経学会学術大会
• [Presentation] 18F-THK5351 PETによる進行性核上性麻痺とパーキンソン病の鑑別の検討 (2019)
  • Author(s): 菊池昭夫、江面道典、岡村信行、長谷川隆文、石木愛子、原田龍一、菅野直人、吉田隼、小林潤平、荒井啓行、谷内一彦、古本 祥三、田代 学、工藤幸司、武田 篤、青木正志
  • Organizer: 第60回日本神経学会学術大会
• [Presentation] 大脳皮質基底核症候群における18F-THK5351 PETの経時的変化 (2018)
  • Author(s): 菊池昭夫、江面道典、岡村信行、長谷川隆文、石木愛子、原田龍一、菅野直人、吉田隼、小林潤平、荒井啓行、谷内一彦、古本 祥三、田代 学、工藤幸司、武田 篤、青木正志
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] 大脳皮質基底核症候群における18F-THK5351 PETの経時的変化 (2017)
  • Author(s): 菊池昭夫、江面道典、岡村信行、長谷川隆文、石木愛子、原田龍一、荒井啓行、谷内一彦、古本 祥三、田代 学、工藤幸司、武田 篤、青木正志
  • Organizer: 第36回日本認知症学会
• [Presentation] 18F-THK5351 PET in corticobasal syndrome (2017)
  • Author(s): Kikuchi A, Okamura N, Hasegawa T, Ezura M, Baba T, Sugeno N, Yoshida S, Kobayashi J, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research