In vivo visualization of synuclein deposition in multiple system atrophy and its clinical applicability

• Project/Area Number: 23591266
• 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, 大学病院, 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 東北大学, 医学系研究科, 准教授 (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, 助教 (50261491)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 多系統萎縮症 / パーキンソン病 / PET / [11C]BF-227 / α-シヌクレイン

Outline of Final Research Achievements

The histopathological hallmark of multiple system atrophy (MSA) is the appearance of glial cytoplasmic inclusions, which are mainly composed of α-synuclein fibrils. We aimed to study whether [11C] 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy) benzoxazole (BF-227) positron emission tomography (PET) can show time-dependent changes of α-synuclein deposits in brain lesions in four MSA with predominant cerebellar ataxia (MSA-C) patients using the Easy Z-Score Imaging System software. [11C]BF-227 PET showed time-dependent increases of tracer uptake in brain lesions such as the subcortical white matter and from frontal to parietal cortex in all four MSA-C patients. We suggest that [11C]BF-227 PET can be used as a surrogate marker of in vivo α-synuclein deposition in MSA-C.

Research Products

• [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] 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: in press
  • 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
• [Journal Article] T2-hyperintensity of the middle cerebellar peduncles in a patient with SCA7. (2013)
  • Author(s): Yoshida S, Kikuchi A, Tateyama M, Aoki M.
  • Journal Title: Intern Med Volume: 52 Pages: 1433-1444
  • NAID: 130003365655
  • Peer Reviewed
• [Journal Article] Anti-voltage-gated potassium channel antibody is associated with chronic autonomic and sensory neuropathy. (2013)
  • Author(s): Kaneko K, Tano O, Kikuchi A, Hasegawa T, Tateyama M, Yoshioka M, Saito H, Watanabe O, Takeda A, Aoki M.
  • Journal Title: J Neurol Volume: 260 Issue: 1 Pages: 315-317
  • DOI: 10.1007/s00415-012-6730-0
  • Peer Reviewed
• [Journal Article] Hypometabolism in the supplementary and anterior cingulate cortices is related to dysphagia in Parkinson's disease: a cross-sectional and 3-year longitudinal cohort study (2013)
  • Author(s): Akio Kikuchi, Toru Baba, Takafumi Hasegawa, Michiko Kobayashi, Naoto Sugeno, Masatoshi Konno, Emiko Miura, Yoshiyuki Hosokai, Toshiyuki Ishioka, Yoshiyuki Nishio, Kazumi Hirayama, Kyoko Suzuki, Masashi Aoki, ShokiTakahashi, Hiroshi Fukuda, Yasuto Itoyama, Etsuro Mori, Atsushi Takeda
  • Journal Title: BMJ Open Volume: 3 Issue: 3 Pages: e002249-e002249
  • DOI: 10.1136/bmjopen-2012-002249
  • Peer Reviewed
• [Journal Article] Suppression of dynamin GTPase decreases alpha-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy. (2012)
  • Author(s): Konno M, Hasegawa T, Baba T, Miura E, Sugeno N, Kikuchi A, Fiesel FC, Sasaki T, Aoki M, Itoyama Y, Takeda A.
  • Journal Title: Mol Neurodegener Volume: 7 Issue: 1 Pages: 38-38
  • DOI: 10.1186/1750-1326-7-38
  • Peer Reviewed
• [Journal Article] Severe olfactory dysfunction is a prodromal symptom of dementia associated with Parkinson’s disease: a 3-year longitudinal study. (2012)
  • Author(s): Baba T, Kikuchi A, Hirayama K, Nishio Y, Hosokai Y, Kanno S, Hasegawa T, Sugeno N, Konno M, Suzuki K, Takahashi S, Fukuda H, Aoki M, Itoyama Y, Mori E, Takeda A.
  • Journal Title: Brain Volume: 135 Pages: 161-169
  • Peer Reviewed
• [Journal Article] Association of olfactory dysfunction and brain. Metabolism in Parkinson’s disease. (2011)
  • Author(s): Baba T, Takeda A, Kikuchi A, Nishio Y, Hosokai Y, Hirayama K, Hasegawa T, Sugeno N, Suzuki K, Mori E, Takahashi S, Fukuda H, Itoyama Y.
  • Journal Title: Mov Disord Volume: 26 Pages: 621-628
  • Peer Reviewed
• [Journal Article] Differentiating Parkinson’s disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test. (2011)
  • Author(s): Kikuchi A, Baba T, Hasegawa T, Sugeno N, Konno M, Takeda A.
  • Journal Title: Parkinsonism Relat Disord Volume: 17 Pages: 698-700
  • Peer Reviewed
• [Journal Article] The AAA-ATPase VPS4 Regulates Extracellular Secretion and Lysosomal Targeting of α-Synuclein. (2011)
  • Author(s): Hasegawa T, Konno M, Baba T, Sugeno N, Kikuchi A, Kobayashi M, Miura E, Tanaka N, Tamai K, Furukawa K, Arai H, Mori F, Wakabayashi K, Aoki M, Itoyama Y, Takeda A.
  • Journal Title: PLoS ONE Volume: 6
  • Peer Reviewed
• [Journal Article] Parkinson病の運動症状発症に先行する非運動症状 ー嗅覚障害ー (2011)
  • Author(s): 馬場徹、菊池昭夫、長谷川隆文、武田篤
  • Journal Title: 神経内科 Volume: 75 Pages: 319-323
• [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
• [Presentation] パーキンソン病の嚥下障害と脳代謝の関係（縦断研究） (2013)
  • Author(s): 菊池昭夫、馬場 徹、長谷川隆文、小林理子、菅野直人、今野昌俊、三浦永美子、西尾慶之、平山和美、鈴木匡子、青木正志、高橋昭喜、福田 寛、糸山泰人、森 悦朗、武田 篤
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] Differentiating Parkinson’s disease from multiple system atrophy by [123I]meta-iodobenzylguanidine myocardial scintigraphy and olfactory test (2013)
  • Author(s): Kikuchi A, Baba T, Hasegawa T, Sugeno N, Konno M, Miura E, Aoki M, Takeda A
  • Organizer: The Movement Disorder Society's 17th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] パーキンソン病の嚥下障害と脳代謝の関係（縦断研究） (2013)
  • Author(s): 菊池昭夫、馬場 徹、長谷川隆文、小林理子、菅野直人、今野昌俊、三浦永美子、西尾慶之、平山和美、鈴木匡子、青木正志、高橋昭喜、福田 寛、糸山泰人、森 悦朗、武田 篤
  • Organizer: 第7回日本パーキンソン病・運動障害疾患コングレス
  • Place of Presentation: 東京
• [Presentation] MIBG心筋シンチグラフィーと嗅覚テストによるパーキンソン病と多系統萎縮症の鑑別 (2012)
  • 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、青木正志、武田篤
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] Hypometabolism in the supplementary and anterior cingulate cortices is related to dysphagia in Parkinson’s disease: a 3-year longitudinal study (2012)
  • Author(s): Kikuchi A, Baba T, Hasegawa T, et al.
  • Organizer: The Movement Disorder Society's 16th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] MIBG心筋シンチグラフィーと嗅覚テストによるパーキンソン病と多系統萎縮症の鑑別 (2012)
  • 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、青木正志、武田篤
  • Organizer: 第6回日本パーキンソン病・運動障害疾患コングレス
  • Place of Presentation: 京都
• [Presentation] 多系統萎縮症における[11C]BF-227 PETの経時的変化 (2011)
  • Author(s): 菊池昭夫
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
• [Presentation] 多系統萎縮症における[11C]BF-227 PETの経時的変化 (2011)
  • Author(s): 菊池昭夫
  • Organizer: 第5回日本パーキンソン病・運動障害疾患コングレス
  • Place of Presentation: 東京
• [Presentation] In vivo visualization of α-synuclein deposition by [11C]-BF-227 PET in multiple system atrophy. (2011)
  • Author(s): Kikuchi A
  • Organizer: The Movement Disorder Society's 15th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Toronto, Canada