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molecular pathological study of pripheral- type Lewy body disease

Research Project

Project/Area Number 22K07550
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Principal Investigator

齊藤 祐子  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (60344066)

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords黒質 / レビー小体 / 認知症 / Lewy body / alpha- synuclein / pure autonomic failure / Parkinson disease / dementia with Lewy body
Outline of Research at the Start

研究リソースの欠如で研究がほとんど行われて来なかった、末梢型Lewy小体を、形態学的研究に加え、蛋白化学、マウスへの伝播実験を含む分子病理学的検討を加えることで、中枢型・脳幹型レビー小体を含めた、Lewy小体病全体における生物学的意義を追求する。対象は、高齢者ブレインバンク登録例で、中枢・末梢の網羅的スクリーニングにより、Lewy小体病理の出現と伝播形式を、中枢、脳幹に末梢を加え検討する。さらに末梢型レビー小体について、免疫組織科学的、超微形態的検討を加える。さらに高度蓄積例に、Western blot、マウスへの伝播実験における、比較検討を加える。

Outline of Annual Research Achievements

【目的】純粋自律神経不全症 (pure autonomic failure: PAF)は,レビー小体病理を背景とする,孤発性,成人発症,緩徐進行性の自律神経系の変性疾患であり,臨床的には起立性低血圧,膀胱・性機能障害などの自律神経症状を示すが,ほかの神経症状は伴わない.当施設で長期経過を観察し,剖検をえられた2例の特徴を検討する.【方法】症例1は死亡時88歳男性である.60代から頻回なめまいとふらつき,失神があり,便秘,発汗障害,嗅覚低下も出現した.途中,軽度認知機能障害を指摘された.その後,心原性脳塞栓症を発症,嚥下性肺炎で死亡した.症例2は死亡時85歳男性である.73歳時に高度の便秘と動揺性血圧が出現,81歳頃から,起立性低血圧や尿失禁,夜間徘徊が出現した.85歳時には認知機能低下が指摘され,同年,尿路感染症により死亡した.【結果】両症例ともに,肉眼所見では青斑核に高度の脱色素を認めたが,中脳黒質の脱色素は比較的軽度であった.組織学的には副腎周囲脂肪織内神経束や交感神経節,中間外側核や後根神経節,迷走神経背側核,延髄網様体,背側縫線核,青斑核,黒質,視床下部,島回,マイネルト基底核,移行嗅内野,海馬CA2,前帯状回,前頭・側頭・頭頂葉にレビー小体病理を認め,DLBコンセンサスガイドラインで辺縁系ないしは新皮質型に該当する広がりであった.【結論】両症例は,我々が提唱して
いるレビー小体病理の進展仮説であるbrain-first versus body-first仮説においては後者に該当するが,黒質が比較的保たれていたことが特徴である.また,海馬CA2のレビー小体病理が相対的に強い点は,PAFの晩期には認知機能にも留意が必要であることを支持する所見である.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

結果が出ており、さらに同様の症例が追加され、データが増えてきており、順調である。

Strategy for Future Research Activity

他のコホートで、対象疾患が多いことがわかり、研究に広がりが出た。そちらの検索も進めたい。また、過去の症例の網羅的なレビー小体の広がりについて、多数例で検討し、PAFの特徴を明らかにする。

Report

(2 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (13 results)

All 2024 2023 2022 2021

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (2 results)

  • [Journal Article] Neuropathological changes associated with aberrant cerebrospinal fluid p-tau181 and Aβ42 in Alzheimer’s disease and other neurodegenerative diseases2024

    • Author(s)
      Kurihara Masanori、Matsubara Tomoyasu、Morimoto Satoru、Arakawa Akira、Ohse Kensuke、Kanemaru Kazutomi、Iwata Atsushi、Murayama Shigeo、Saito Yuko
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 12 Issue: 1 Pages: 48-48

    • DOI

      10.1186/s40478-024-01758-3

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An autopsy case of variably protease‐sensitive prionopathy with Met/Met homogeneity at codon 1292023

    • Author(s)
      Uchino Akiko、Saito Yuko、Oonuma Saori、Murayama Shigeo、Yagishita Saburo、Kitamoto Tetsuyuki、Hasegawa Kazuko
    • Journal Title

      Neuropathology

      Volume: 43 Issue: 6 Pages: 486-495

    • DOI

      10.1111/neup.12911

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cryo‐EM structures of tau filaments from SH‐SY5Y cells seeded with brain extracts from cases of Alzheimer's disease and corticobasal degeneration2023

    • Author(s)
      Tarutani Airi、Lovestam Sofia、Zhang Xianjun、Kotecha Abhay、Robinson Andrew C.、Mann David M. A.、Saito Yuko、Murayama Shigeo、Tomita Taisuke、Goedert Michel、Scheres Sjors H. W.、Hasegawa Masato
    • Journal Title

      FEBS Open Bio

      Volume: 13 Issue: 8 Pages: 1394-1404

    • DOI

      10.1002/2211-5463.13657

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Parkinson’s disease in a patient with olfactory hypoplasia: a model case of “body-first Lewy body disease” providing insights into the progression of α-synuclein accumulation2023

    • Author(s)
      Matsubara Tomoyasu、Murayama Shigeo、Tsukamoto Tadashi、Sano Terunori、Mizutani Masashi、Tanei Zen-ichi、Takahashi Yuji、Takao Masaki、Saito Yuko
    • Journal Title

      Journal of Neurology

      Volume: 270 Issue: 10 Pages: 5090-5093

    • DOI

      10.1007/s00415-023-11783-2

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Correlations between cerebrospinal fluid homovanillic acid and dopamine transporter SPECT in degenerative parkinsonian syndromes2023

    • Author(s)
      Goto Ryoji、Kurihara Masanori、Kameyama Masashi、Komatsu Hiroki、Higashino Masashi、Hatano Keiko、Ihara Ryoko、Higashihara Mana、Nishina Yasushi、Matsubara Tomoyasu、Kanemaru Kazutomi、Saito Yuko、Murayama Shigeo、Iwata Atsushi
    • Journal Title

      Journal of Neural Transmission

      Volume: 130 Issue: 4 Pages: 513-520

    • DOI

      10.1007/s00702-023-02611-y

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Astrocytic APOE4 genotype-mediated negative impacts on synaptic architecture in human pluripotent stem cell model2023

    • Author(s)
      Watanabe Hirotaka、Murakami Rei、Tsumagari Kazuya、Morimoto Satoru、Hashimoto Tadafumi、Imaizumi Kent、Sonn Iki、Yamada Kaoru、Saito Yuko、Murayama Shigeo、Iwatsubo Takeshi、Okano Hideyuki
    • Journal Title

      Stem Cell Reports

      Volume: 18 Issue: 9 Pages: 1854-1869

    • DOI

      10.1016/j.stemcr.2023.08.002

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Erdheim-Chester Disease Involving the Central Nervous System with Latent Toxoplasmosis2022

    • Author(s)
      Wadayama Tomoya、Shimizu Mikito、Kimura Ikko、Baba Kousuke、Beck Goichi、Nagano Seiichi、Morita Ryo、Nakagawa Hidenori、Shirano Michinori、Goto Tetsushi、Norose Kazumi、Hikosaka Kenji、Murayama Shigeo、Mochizuki Hideki
    • Journal Title

      Internal Medicine

      Volume: 61 Issue: 17 Pages: 2661-2666

    • DOI

      10.2169/internalmedicine.8564-21

    • NAID

      130008158352

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2022-09-01
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathology-associated change in levels and localization of SIDT2 in postmortem brains of Parkinson's disease and dementia with Lewy bodies patients2022

    • Author(s)
      Fujiwara Yuuki、Kabuta Chihana、Sano Terunori、Murayama Shigeo、Saito Yuko、Kabuta Tomohiro
    • Journal Title

      Neurochemistry International

      Volume: 152 Pages: 105243-105243

    • DOI

      10.1016/j.neuint.2021.105243

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis2022

    • Author(s)
      Abdelhamid Rehab F.、Ogawa Kotaro、Beck Goichi、Ikenaka Kensuke、Takeuchi Eriko、Yasumizu Yoshiaki、Jinno Jyunki、Kimura Yasuyoshi、Baba Kousuke、Nagai Yoshitaka、Okada Yukinori、Saito Yuko、Murayama Shigeo、Mochizuki Hideki、Nagano Seiichi
    • Journal Title

      Molecular Neurobiology

      Volume: 59 Issue: 3 Pages: 1693-1705

    • DOI

      10.1007/s12035-021-02686-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thymidine kinase 2 and mitochondrial protein COX I in the cerebellum of patients with spinocerebellar ataxia type 31 caused by penta-nucleotide repeats (TTCCA) n.2022

    • Author(s)
      Aoki H, Higashi M, Okita M, Ando N, Murayama S, Ishikawa K*, Yokota T.
    • Journal Title

      Cerebellum.

      Volume: Jan 27 Issue: 1 Pages: 70-84

    • DOI

      10.1007/s12311-021-01364-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lemur tail kinase 1 (LMTK1) regulates the endosomal localization of β-secretase BACE12021

    • Author(s)
      Komaki Keisuke、Takano Tetsuya、Sato Yutaka、Asada Akiko、Ikeda Shikito、Yamada Kaoru、Wei Ran、Huo Anni、Fukuchi Aoi、Saito Taro、Ando Kanae、Murayama Shigeo、Araki Wataru、Kametani Fuyuki、Hasegawa Masato、Iwatsubo Takeshi、Tomomura Mineko、Fukuda Mitsunori、Hisanaga Shin-ichi
    • Journal Title

      The Journal of Biochemistry

      Volume: 170 Issue: 6 Pages: 729-738

    • DOI

      10.1093/jb/mvab094

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] ALSの長期生存例2023

    • Author(s)
      齊藤祐子、金丸一富、德丸阿弥、村山繁雄
    • Organizer
      第64回日本神経病理学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 純粋自立神経不全症の神経病理学的検討2023

    • Author(s)
      原愛徒、齊藤祐子、村山繁雄
    • Organizer
      第76回日本自律神経学会
    • Related Report
      2023 Research-status Report

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Published: 2022-04-19   Modified: 2024-12-25  

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