シヌクレイノパチーの分子イメージング

• Project Area: Brain Environment
• Project/Area Number: 24111502
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: 武田 篤 東北大学, 医学(系)研究科(研究院), 非常勤講師 (70261534)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: シヌクレイノパチー / レビー小体 / グリア細胞質封入体 / パーキンソン病 / 多系統萎縮症 / レビー小体型認知症 / 分子イメージング / BF-227

Research Abstract

多系統萎縮症の新たな画像検査法としてBF-227 PETの臨床応用可能性をさらに詳細に検討した。まず特異性と感度を明らかとするために対象症例を増やしてデータの蓄積を図り、MRIやその他の画像所見とも比較・検討、病期による経年変化検討した。多系統萎縮症は主にパーキンソニズムを主とする群（MSA-P）と小脳失調を主とする群（MSA-C）に分類されるが、こうした臨床症候による違い、さらに各臨床症候（錐体路症候、パーキンソニズム、小脳失調、自律神経障害など）の重症度と脳部位別に見たBF-227結合性の分布との関連性も検討した。
結果として病期の進行に伴ない多系統萎縮症に於けるシヌクレインの沈着は初期に増加し、中期以降には徐々に低下
する可能性が示唆された。MSA-PとMSA-C間の相違は明らかでなかった。
また同じシヌクレイノパチーであるパーキンソン病について症例をエントリーしBF-227による脳画像の検討を開始した。この結果、パーキンソン病に於けるシヌクレイン沈着様式に大きく2つのパターンがある可能性を示唆するデータが得られた。全体の約半数はほとんどBF-227の脳内集積を認めなかった（低集積群）が、残りの半数は、広範な大脳皮質に集積を認めた（高集積群）。特に大脳辺縁系への集積が顕著であり、これらはレビー小体型認知症に於けるレビー小体の分布に類似するものであった。パーキンソン病に於けるレビー小体病理の進展様式には、脳幹を主とするものと嗅球や大脳辺縁系を中心とするものの二つの進展経路があり、前者は運動症状や自律神経症状に関連し、後者は嗅覚低下や認知機能低下に関係すると言う仮説が、病理学的検討や臨床的な縦断研究から示唆されて来ているが、今回の結果はこうした考えと良く一致するものと言える。

Current Status of Research Progress

Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

Research Products

• [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] Pathogenesis of Multiple system atrophy. (2013)
  • Author(s): Hasegawa T, Kikuchi A, Takeda A.
  • Journal Title: Neurol Clin Neurosci Volume: 1 (6) Issue: 6 Pages: 189-194
  • DOI: 10.1111/ncn3.57
  • 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): BabaT, Kikuchi A, Hirayama K, Nishio Y, Hosokai Y, Kanno S, Hasegawa T, Sugeno N, Konno M, Suzuki K, et al
  • Journal Title: Brain Volume: 135 Issue: 1 Pages: 162-169
  • DOI: 10.1093/brain/awr321
  • Peer Reviewed
• [Journal Article] Attentional Set-Shifting Deficit in Parkinson's Disease Is Associated with Prefrontal Dysfunction: An FDG-PET Study (2012)
  • Author(s): Yoichi Sawada, Yoshiyuki Nishio, Kyoko Suzuki, Kazumi Hirayama, Atsushi Takeda, Yoshiyuki Hosokai, Toshiyuki Ishioka, Yasuto Itoyama, Shoki Takahashi, Hiroshi Fukuda, Etsuro Mori
  • Journal Title: PLoS ONE Volume: 7(6) Issue: 6 Pages: e38498-e38498
  • DOI: 10.1371/journal.pone.0038498
  • Peer Reviewed
• [Journal Article] Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia (2012)
  • Author(s): Hiraoka K, Okamura N, Funaki Y, Hayashi A, Tashiro M, Hisanaga K, Fujii T, Takeda A, Y anai K, Iwata R, Mori E
  • Journal Title: Eur Neurol Volume: 68 Issue: 3 Pages: 137-143
  • DOI: 10.1159/000338774
  • 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
• [Presentation] Severe hyposmia is a prodromal symptom of dementia in Parkinson disease (2013)
  • Author(s): Takeda A.
  • Organizer: 9th International congress on mental dysfunction & other non-motor features in Parkinson’s disease and related disorders
  • Place of Presentation: Seoul, South Korea
  • Invited
• [Presentation] 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. Aoki M. Takeda A.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders, Sydney, Australia, 2013
  • Place of Presentation: Sydney, Australia
• [Presentation] Nedd4 E3 ubiquitin ligase facilitates the endosomal targeting of alpha-synuclein (2013)
  • Author(s): Sugeno N. Hasegawa T. Konno M. Miura E. Kikuchi A. Aoki M. Takeda A.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders, Sydney, Australia, 2013
  • Place of Presentation: Sydney, Australia
• [Presentation] ., RNAi-mediated knockdown of VPS35 impairs α-synuclein degradation by inhibiting the maturation of cathepsin D (2013)
  • Author(s): 62) Miura E. Hasegawa T. Konno M. Sugeno N. Kikuchi A. Baba T. Aoki M. Takeda A.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders, Sydney, Australia, 2013
  • Place of Presentation: Sydney, Australia
• [Presentation] RNAi-mediated silencing of VPS35 exacerbates phenotypic and locomotor abnormalities in α-synuclein transgenic drosophila (2013)
  • Author(s): Hasegawa T. Konno M. Miura E. Sugeno N. Nagai Y. Fujikake N. Suzuki M. Kikuchi A. Aoki M. Takeda A.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders, Sydney, Australia, 2013
  • Place of Presentation: Sydney, Australia
• [Presentation] Search for rare-variant risks of Parkinson's disease by sequencing of candidate genes and exome sequencing (2013)
  • Author(s): Satake W. Ando Y. Tomiyama H. Takeda A. Hasegawa K. Yamamoto M. Murata M. Hattori N. Toda T.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders, Sydney, Australia, 2013
  • Place of Presentation: Sydney, Australia
• [Presentation] The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting of α-synuclein (2012)
  • Author(s): Hasegawa T., Konno M., Baba T., Sugeno N., Kikuchi A., Miura E., Takeda A.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 2012-06-17
• [Presentation] Severe olfactory dysfunction is predictive 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., Miura E., Mori E., Takeda A.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 2012-06-17
• [Presentation] Dynamin GTPase activity decreases alpha-synuclein uptake in neuronal and oligodendroglial cells (2012)
  • Author(s): Konno M., Hasegawa T., Baba T., Miura E., Sugeno N., Kikuchi A., Aoki M., Takeda A.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 2012-06-17
• [Presentation] Nedd4 participates in the internalization process of alpha-synuclein (2012)
  • Author(s): Sugeno N., Hasegawa T., Konno M., Miura E., Baba T., Kikuchi A., Aoki M., Takeda A.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 2012-06-17
• [Presentation] Neural basis of memory impairment in Parkinson’s disease: A longitudinal PET study (2012)
  • Author(s): Shoji Y., Nishio Y., Takeda A., Uchiyama M., Kashinoura T., Hosokai Y., Fukuda H., Mori E.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 2012-06-17
• [Presentation] Japanese 2nd GWAS identifies strong association at a novel risk locus and MCCC1 for Parkinson’s disease (2012)
  • Author(s): Satake W., Yamamoto K., Ando Y., Takeda A., et al.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 2012-06-17