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

• Project/Area Number: 26461303
• 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, 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: ¥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.

Research Products

• [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] 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] 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
• [Journal Article] Brain Metabolic Changes of Cervical Dystonia with Spinocerebellar Ataxia Type 1 after Botulinum Toxin Therapy (2016)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Subgroup differences in “brain-type” transferrin and alpha-synuclein in Parkinson's disease and multiple system atrophy (2016)
  • 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
  • Peer Reviewed
• [Journal Article] On the utility of MIBG SPECT/CT in evaluating cardiac sympathetic dysfunction in Lewy body diseases (2016)
  • 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
  • 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 pathways (2016)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Variants associated with Gaucher disease in multiple system atrophy. (2015)
  • 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: 417-426
  • DOI: 10.1002/acn3.185
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
  • Invited
• [Presentation] Assessment of tau pathology in patients with corticobasal syndrome using 18F-THK5351 PET (2016)
  • 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
  • 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
• [Presentation] Longitudinal [11C]BF-227 PET study in MSA-C patients (2015)
  • 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
  • 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
• [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
• [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