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In vivo visualization of synuclein deposits in Parkinson's disease and its clinical applicability

Research Project

Project/Area Number 26461303
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionTohoku University

Principal Investigator

Kikuchi Akio  東北大学, 医学系研究科, 助教 (80463785)

Research Collaborator TAKEDA Atsushi  独立行政法人国立病院機構, 仙台西多賀病院, 院長 (70261534)
OKAMURA Nobuyuki  東北医科薬科大学, 医学部, 教授 (40361076)
FURUMOTO Shozo  東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00375198)
TASHIRO Manabu  東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00333477)
FUNAKI Yoshihito  東北大学, サイクロトロン・ラジオアイソトープセンター, 講師 (50261491)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsパーキンソン病 / PET / [11C] BF-227 / α-シヌクレイン / [11C]BF-227
Outline of Final Research Achievements

The histopathological hallmark of Parkinson's disease (PD) is the appearance of Lewy bodies, which are mainly composed of α-synuclein fibrils. In vivo visualization of α-synuclein depositis should be for the assessment of therapy and severity of pathological progression in PD. We aimed to evaluate whether carbon-11-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy) benzoxazole ([11C] BF-227) positron emission tomography (PET) can detect α-synuclein deposits in patients with PD. PD patients showed high uptake in precentral and postcentral cortices compared to normal controls. [11C] BF-227 showed time-dependent increases of tracer uptake in amygdala, anterior cingulate cortex, insula and globus pallidus, etc., in PD patients. Our data suggest that [11C] BF-227 PET can detect α-synuclein deposits and be used as a surrogate marker in PD patients.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (24 results)

All 2018 2017 2016 2015 2014 2013

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 7 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [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

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Membrane Trafficking Illuminates a Path to Parkinson’s Disease2017

    • 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
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brain Metabolic Changes of Cervical Dystonia with Spinocerebellar Ataxia Type 1 after Botulinum Toxin Therapy2016

    • Author(s)
      Kikuchi A, Takeda A, Sugeno N, Miura E, Kato K, Hasegawa T, Baba T, Konno M, Oshima R, Watanuki S, Hiraoka K, Tashiro M, Aoki M
    • Journal Title

      Internal Medicine

      Volume: 55 Issue: 14 Pages: 1919-1922

    • DOI

      10.2169/internalmedicine.55.5843

    • NAID

      130005164997

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Subgroup differences in “brain-type” transferrin and alpha-synuclein in Parkinson's disease and multiple system atrophy2016

    • Author(s)
      A Yoshihara, M Fukatsu, K Hoshi, Y Hashimoto, et. al
    • Journal Title

      The Journal of Biochemistry

      Volume: 159 Issue: 2 Pages: 87-91

    • DOI

      10.1093/jb/mvw015

    • Description
      未定
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] On the utility of MIBG SPECT/CT in evaluating cardiac sympathetic dysfunction in Lewy body diseases2016

    • Author(s)
      Odagiri H, Baba T, Nishio Y, Iizuka O, Matsuda M, Inoue K, Kikuchi A, Hasegawa T, Aoki M, Takeda A, Taki Y, Mori E
    • Journal Title

      PLoS One

      Volume: 11(4) Issue: 4 Pages: 0152746-0152746

    • DOI

      10.1371/journal.pone.0152746

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways2016

    • Author(s)
      Oshima R, Hasegawa T, Tamai K, Sugeno N, Yoshida S, Kobayashi J, Kikuchi A, Baba T, Futatsugi A, Sato I, Satoh K, Takeda A, Aoki M and Tanaka N
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 24997-24997

    • DOI

      10.1038/srep24997

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] In vivo visualization of tau pathology using 18F-THK5351 PET in corticobasal syndrome.2016

    • Author(s)
      Kikuchi A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Kobayashi M, Tano O, Baba T, Sugeno N, Oshima R, Yoshida S, Kobayashi J, Ezura M, Hiraoka K, Mugikura S, Takase K, Iwata R, Taki Y, Furukawa K, HArai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A,Aoki M.
    • Journal Title

      Neurology

      Volume: 87 Issue: 22 Pages: 2309-2316

    • DOI

      10.1212/wnl.0000000000003375

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Variants associated with Gaucher disease in multiple system atrophy2015

    • Author(s)
      Mitsui J, Matsukawa T, Sasaki H, Yabe I, Nakahara Y, Momose Y, Takahashi Y, Hara K, Kakita A, Yamada M, Takahashi H, Onodera O, Nishizawa M, Watanabe H, Nakashima K, Ito H, Izumi Y, Kaji R, Kato T, Tsuji S, et al.
    • Journal Title

      Ann Clin Transl Neurol.

      Volume: 2 Issue: 4 Pages: 417

    • DOI

      10.1002/acn3.185

    • URL

      https://localhost/en/publications/c946bad2-a238-4d0e-a396-6d33b3922ab7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] VPS35 dysfunction impairs lysosomal degradation of α-synuclein and exacerbates neurotoxicity in a Drosophila model of Parkinson's disease.2014

    • Author(s)
      Miura E, Hasegawa T, Konno M, Suzuki M, Sugeno N, Fujikake N, Geisler S, Tabuchi M, Oshima R, Kikuchi A, Baba T, Wada K, Nagai Y, Takeda A, Aoki M.
    • Journal Title

      Neurobio Dis

      Volume: 71 Pages: 1-13

    • DOI

      10.1016/j.nbd.2014.07.014

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] K63-linked ubiquitination by E3 Ubiquitin Ligase Nedd4-1 facilitates endosomal sequestration of internalized alpha-synuclein.2014

    • Author(s)
      Sugeno N, Hasegawa T, Tanaka N, Fukuda M, Wakabayashi K, Oshima R, Konno M, Miura E, Kikuchi A, Baba T, Anan T, Nakao M, Geisler S, Aoki M, Takeda A.
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 26 Pages: 18137-18151

    • DOI

      10.1074/jbc.m113.529461

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement of freezing of gait in patients with Parkinson’s disease by imagining bicycling.2014

    • Author(s)
      Kikuchi A, Baba T, Hasegawa T, Sugeno N, Konno M, Miura E, Oshima R, Aoki M, Takeda A.
    • Journal Title

      Case Rep Neurol

      Volume: 6 Issue: 1 Pages: 92-95

    • DOI

      10.1159/000362119

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Olfactory dysfunction and dementia in Parkinson's disease.2014

    • Author(s)
      Takeda A, Baba T, Kikuchi A, Hasegawa T, Sugeno N, Konno M, Miura E, Mori E.
    • Journal Title

      J Parkinsons Dis

      Volume: 4 Issue: 2 Pages: 181-187

    • DOI

      10.3233/jpd-130277

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathogenesis of multiple system atrophy.2013

    • Author(s)
      Hasegawa T, Kikuchi A, Takeda A.
    • Journal Title

      Neurology and Clinical Neuroscience

      Volume: 1 Issue: 4 Pages: 189-194

    • DOI

      10.1007/s00415-014-7271-5

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [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
    • Related Report
      2017 Annual Research Report
  • [Presentation] 18F-THK5351 PET in corticobasal syndrome2017

    • 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
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経変性疾患におけるPETの最近の話題2016

    • Author(s)
      菊池昭夫
    • Organizer
      第10回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      京都、京都ホテルオークラ
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Assessment of tau pathology in patients with corticobasal syndrome using 18F-THK5351 PET2016

    • Author(s)
      Kikuchi A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Toru Baba, Naoto Sugeno, Ryuji Oshima, Shun Yoshida, Junpei Kobayashi, Ezura M, Kobayashi M, Tano O, Mugikura S, Iwata R, Ishiki A, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
    • Organizer
      The Movement Disorder Society's 20th International Congress of Parkinson's Disease and Movement Disorders
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2016-06-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] パーキンソン病患者での[11C]BF-227 PETによるα-シヌクレイン蛋白凝集体の画像化2016

    • Author(s)
      菊池昭夫、岡村信行、馬場 徹、長谷川隆文、菅野直人、大嶋龍司、吉田隼、小林潤平、平岡宏太良、古本祥三、谷内一彦、田代 学、工藤幸司、武田 篤、青木正志
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸、神戸コンベンションセンター・神戸ポートピアホテル
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Longitudinal [11C]BF-227 PET study in MSA-C patients2015

    • Author(s)
      Kikuchi A, Okamura N, Tashiro M, Furumoto S, Hasegawa T, Watanuki S, Hiraoka K, Funaki Y, Kobayashi M, Sugeno N, Baba T, Konno M, Miura E, Oshima R, Yoshida S, Iwata R, Takahashi S, Fukuda H, Itoyama Y, Arai H, Kudo Y, Yanai K, Aoki M, Takeda A.
    • Organizer
      19th International Congress of Parkinson's Disease and Movement Disorders
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-06-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] [11C]BF-227 PETにおける多系統萎縮症脳内α-シヌクレインの経時的変化2015

    • Author(s)
      菊池昭夫、岡村信行、馬場 徹、長谷川隆文、菅野直人、今野昌俊、三浦永美子、大嶋龍司、吉田隼、古本祥三、平岡宏太良、谷内一彦、田代 学、工藤幸司、糸山泰人、武田 篤、青木正志.
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      朱鷺メッセ (新潟)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report
  • [Presentation] [11C] BF-227 PET can visualize in vivo α-synuclein deposition in Parkinson’s disease.2014

    • Author(s)
      Kikuchi A, Okamura N, Tashiro M, Hasegawa T, Sugeno N, Baba T, Konno M, Miura E, Oshima R, Furumoto S, Funaki Y, Iwata R, Takahashi S, Fukuda H, Arai H, Kudo Y, Yanai K, Aoki M, Itoyama Y, Takeda A.
    • Organizer
      18th International Congress of Parkinson's Disease and Movement Disorders
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2014-06-08 – 2014-06-12
    • Related Report
      2014 Research-status Report
  • [Presentation] パーキンソン病における脳内α-シヌクレイン蛋白凝集体のPETによる画像化.2014

    • Author(s)
      菊池昭夫、馬場 徹、長谷川隆文、菅野直人、今野昌俊、三浦永美子、大嶋龍司、岡村信行、古本祥三、谷内一彦、田代 学、工藤幸司、糸山泰人、武田 篤、青木正志.
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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