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Study on transmission of Abeta aggregates and its prevention

Research Project

Project/Area Number 17H04194
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKanazawa University

Principal Investigator

Yamada Masahito  金沢大学, 医学系, 教授 (80191336)

Co-Investigator(Kenkyū-buntansha) 濱口 毅  金沢大学, 医学系, 准教授 (70452109)
坂井 健二  金沢大学, 附属病院, 講師 (00572306)
池田 篤平  金沢大学, 医学系, 協力研究員 (30755773)
中山 隆宏  金沢大学, ナノ生命科学研究所, 准教授 (00532821)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywordsアルツハイマー病 / アミロイドβ蛋白 / 伝播 / 防御 / 凝集 / オートクレーブ処理 / γ線照射 / アミロイドβタンパク
Outline of Final Research Achievements

Studies with thioflavin T (ThT) assays and high-speed atomic force microscopy revealed that seeding effect of amyloid β-protein (Aβ) aggregates was inactivated by autoclave (AC), depending on different temperatures, exposure times, and concentrations of Aβ aggregates at the treatment with AC. Seeding activity of Aβ40 aggregates was more easily inactivated by AC at the same conditions compared to that of Aβ42 aggregates. Results of ThT fluorescence and circular dichroism spectral patterns of autoclaved Aβ aggregates indicated that AC reduced β-sheet-rich structures in Aβ aggregates. Electron microscopy images demonstrated that lengths of autoclaved Aβ aggregates with fibril-like structures was significantly shorter than those of non-treated ones. Gamma-ray irradiation for Aβ aggregates did not inactivate Aβ seeding effect or induce structural changes of Aβ aggregates significantly.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病の中心的病理所見の1つである老人斑を構成するアミロイドβ蛋白(Aβ)は、動物実験レベルで個体間を伝播することが明らかになっている。また、硬膜移植やヒト下垂体由来成長ホルモン製剤投与といった医療行為を介してAβ病理が個体間を伝播し、時間を経て症候性の脳アミロイドアンギオパチー関連脳出血を引き起こす可能性も示唆されている。本研究では、オートクレーブ(AC)がAβ凝集体のβシート構造を減少させ、seeding効果を低下させることを明らかにした。この結果は、ACがAβ凝集体の個体間伝播を予防しうる可能性を示唆し、本研究成果はAβ凝集体の個体間伝播を抑制する不活化法の開発につながる。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (49 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (19 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 17 results,  Open Access: 9 results) Presentation (18 results) (of which Int'l Joint Research: 6 results,  Invited: 14 results) Book (5 results) Remarks (3 results)

  • [Int'l Joint Research] チュービンゲン大学(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] チュービンゲン大学(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] チュービンゲン大学(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] チュービンゲン大学(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Cerebrospinal fluid cytokines and metalloproteinases in cerebral amyloid angiopathy-related inflammation2021

    • Author(s)
      Sakai K, Noguchi-Shinohara M, Ikeda T, Hamaguchi T, Ono K, Yamada M
    • Journal Title

      Acta Neurol Scand

      Volume: 143 Issue: 4 Pages: 450-457

    • DOI

      10.1111/ane.13382

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rosmarinic acid suppresses tau phosphorylation and cognitive decline by downregulating the JNK signaling pathway.2021

    • Author(s)
      Yamamoto S, Kayama T, Noguchi-Shinohara M, Hamaguchi T, Yamada M, Abe K, Kobayashi S.
    • Journal Title

      npj Science of Food

      Volume: 5 Issue: 1 Pages: 1-1

    • DOI

      10.1038/s41538-021-00084-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spontaneous MEG activity of the cerebral cortex during eyes closed and open discriminates Alzheimer’s disease from cognitively normal older adults2020

    • Author(s)
      Ikeda Yoshihisa、Kikuchi Mitsuru、Noguchi-Shinohara Moeko、Iwasa Kazuo、Kameya Masafumi、Hirosawa Tetsu、Yoshita Mitsuhiro、Ono Kenjiro、Samuraki-Yokohama Miharu、Yamada Masahito
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 9132-9132

    • DOI

      10.1038/s41598-020-66034-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Costs and resource use associated with community-dwelling patients with Alzheimer's disease in Japan: baseline results from the prospective observational GERAS-J study.2020

    • Author(s)
      Nakanishi M, Igarashi A, Ueda K, Brnabic AJM, Treuer T, Sato M, Kahle-Wrobleski K, Meguro K, Yamada M, Mimura M, Arai H.
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 74 Issue: 1 Pages: 127-138

    • DOI

      10.3233/jad-190811

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Study design and baseline characteristics of a population-based prospective cohort study of dementia in Japan: the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD).2020

    • Author(s)
      Ninomiya T, Nakaji S, Maeda T, Yamada M, Mimura M, Nakashima K, Mori T, Takebayashi M, Ohara T, Hata J, Kokubo Y, Uchida K, Taki Y, Kumagai S, Yonemoto K, Yoshida H, Muto K, Momozawa Y, Akiyama M, Kubo M, Ikeda M, Kanba S, Kiyohara Y.
    • Journal Title

      Environmental Health and Preventive Medicine

      Volume: 25 Issue: 1 Pages: 64-64

    • DOI

      10.1186/s12199-020-00903-3

    • NAID

      210000158612

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer’s disease progression2020

    • Author(s)
      Noguchi-Shinohara Moeko、Ono Kenjiro、Hamaguchi Tsuyoshi、Nagai Toshitada、Kobayashi Shoko、Komatsu Junji、Samuraki-Yokohama Miharu、Iwasa Kazuo、Yokoyama Kunihiko、Nakamura Hiroyuki、Yamada Masahito
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 18627-18627

    • DOI

      10.1038/s41598-020-73729-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 脳アミロイドアンギオパチー(脳アミロイド血管症)2020

    • Author(s)
      坂井健二、山田正仁
    • Journal Title

      BIO Clinica

      Volume: 6 Pages: 21-25

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of Sporadic Creutzfeldt-Jakob Disease and History of Neurosurgery to Identify Potential Iatrogenic Cases2020

    • Author(s)
      Hamaguchi Tsuyoshi、Sakai Kenji、Kobayashi Atsushi、Kitamoto Tetsuyuki、Ae Ryusuke、Nakamura Yosikazu、Sanjo Nobuo、Arai Kimihito、Koide Mizuho、Katada Fumiaki、Harada Masafumi、Murai Hiroyuki、Murayama Shigeo、Tsukamoto Tadashi、Mizusawa Hidehiro、Yamada Masahito
    • Journal Title

      Emerging Infectious Diseases

      Volume: 26 Issue: 6 Pages: 1140-1146

    • DOI

      10.3201/eid2606.181969

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of “sporadic CJD” with history of neurosurgery to identify potentially iatrogenic cases.2020

    • Author(s)
      Hamaguchi T, Sakai K, Kobayashi A, Kitamoto T, Ae R, Nakamura Y, Sanjo N, Arai K, Koide M, Katada F, Harada M, Murai H, Murayama S, Tsukamoto T, Mizusawa H, Yamada M.
    • Journal Title

      Emerg Infect Dis

      Volume: in press

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cerebral hemorrhagic stroke associated with cerebral amyloid angiopathy in young adults about 3 decades after neurosurgeries in their infancy.2019

    • Author(s)
      Hamaguchi T, Komatsu J, Sakai K, Noguchi-Shinohara M, Aoki S, Ikeuchi T, Yamada M
    • Journal Title

      J Neurol Sci

      Volume: 399 Pages: 3-5

    • DOI

      10.1016/j.jns.2019.01.051

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Age at onset in genetic prion disease and the design of preventive clinical trials2019

    • Author(s)
      Minikel Eric Vallabh、Kitamoto Tetsuyuki、Mead Simon、et al(32人,18番目)
    • Journal Title

      Neurology

      Volume: 93 Issue: 2

    • DOI

      10.1212/wnl.0000000000007745

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Acquired cerebral amyloid angiopathy: An emerging concept2019

    • Author(s)
      Yamada Masahito、Hamaguchi Tsuyoshi、Sakai Kenji
    • Journal Title

      Prog Mol Biol Transl Sci

      Volume: 168 Pages: 85-95

    • DOI

      10.1016/bs.pmbts.2019.05.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アミロイドβタンパクの伝播2019

    • Author(s)
      濵口 毅、山田正仁
    • Journal Title

      Dementia Japan

      Volume: 33 Pages: 31-38

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] プリオンとプリオン様タンパク質の伝播2019

    • Author(s)
      濵口 毅、山田正仁
    • Journal Title

      老年期認知症研究会誌

      Volume: 22 Pages: 79-86

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 伝播からみたプリオン病と神経変性疾患2019

    • Author(s)
      山田正仁、濵口 毅
    • Journal Title

      日本内科学会雑誌

      Volume: 108 Pages: 1979-1984

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The sulfation code for propagation of neurodegeneration2018

    • Author(s)
      Yamada M, Hamaguchi T
    • Journal Title

      J Biol Chem

      Volume: 293 Issue: 27 Pages: 10841-10842

    • DOI

      10.1074/jbc.h118.003970

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Visualization of Protein Assembly Dynamics by Using High-speed Atomic Force Microscopy2018

    • Author(s)
      中山隆宏、紺野宏記、山田正仁、小野賢二郎
    • Journal Title

      Seibutsu Butsuri

      Volume: 58 Issue: 2 Pages: 086-088

    • DOI

      10.2142/biophys.58.086

    • NAID

      130006594328

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] アルツハイマー病やパーキンソン病もプリオン病か2017

    • Author(s)
      濵口 毅、山田正仁
    • Journal Title

      Pharma Medica

      Volume: 35 Pages: 59-66

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 医原性Creutzfeldt-Jakob病におけるプリオン及びプリオン様タンパク質の伝播2017

    • Author(s)
      山田正仁
    • Journal Title

      Neuroinfection

      Volume: 22 Pages: 1-5

    • Related Report
      2017 Annual Research Report
  • [Presentation] Transmission of Aβ pathology leading to early-onset cerebral amyloid angiopathy in humans.2020

    • Author(s)
      Yamada M.
    • Organizer
      2nd AAT-AD/PD Focus Meeting 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脳アミロイドアンギオパチーにおける炎症と認知症2020

    • Author(s)
      坂井健二、山田正仁
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 脳間質液の排出障害と脳アミロイドアンギオパチー2020

    • Author(s)
      坂井健二、山田正仁
    • Organizer
      第61回日本神経病理学会総会学術研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Evidence of Aβ propagation in human and animal models.2020

    • Author(s)
      Hamaguchi T, Yamada M.
    • Organizer
      第61回日本神経病理学会総会学術研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病(AD)類似の非AD型認知症と認知症防御因子の研究2020

    • Author(s)
      山田正仁
    • Organizer
      第2回九州大学漢方教育・診療研究会学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 認知症は予防できるのか 専門医からみた予防の視点とエビデンスを考える2020

    • Author(s)
      山田正仁
    • Organizer
      アルツハイマー病研究会第21回特別紙面学術シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病(AD)類似の非タウオパチー2020

    • Author(s)
      山田正仁
    • Organizer
      品川認知症対策協議会 第15回品川認知症勉強会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] アミロイドβ蛋白質のプリオン様伝播2020

    • Author(s)
      山田正仁
    • Organizer
      第35回日本老年精神医学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ヒトにおけるプリオン病と類縁疾患の伝播2019

    • Author(s)
      山田正仁、濵口 毅
    • Organizer
      第60回日本神経病理学会総会学術研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 伝播から見たプリオン病と神経変性疾患2019

    • Author(s)
      山田正仁
    • Organizer
      第116回日本内科学会総会・講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] アミロイドーシスを予防し治療するための基礎と臨床2019

    • Author(s)
      山田正仁
    • Organizer
      第30回日本医学会総会2019中部
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Cross-seeding effect of protein aggregates derived from foods on Aβ deposition in mouse brain.2019

    • Author(s)
      Hamaguchi T, Goto R, Ono K, Yamada M.
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Iatrogenic Aβ transmission.2019

    • Author(s)
      Mizusawa H, Hamaguchi T, Yamada M.
    • Organizer
      24th World Congress of Neurology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinicopathological study of cerebral amyloid angiopathy-related cerebrovascular diseases in young adults about 3 decades after neurosurgeries in the early childhood.2018

    • Author(s)
      Hamaguchi T, Komatsu J, Sakai K, Aoki S, Ikeuchi T, Yamada M.
    • Organizer
      Asian Pacific Prion Symposium 2018(APPS2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transmission of amyloid β protein2017

    • Author(s)
      Hamaguchi T, Yamada M
    • Organizer
      Asian Pacific Prion Symposium (APPS2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Iatrogenic Creutzfeldt-Jakob disease related to dura mater grafts2017

    • Author(s)
      Yamada M, Hamaguchi T, Sakai K, Noguchi-Shinohara M, Nozaki I, Taniguchi Y, Kobayashi A, Takeuchi A, Kitamoto T, Nakamura Y, Sanjo N, Tsukamoto T, Takao M, Murayama S, Iwasaki Y, Yoshida M, Shimizu H, Kakita A, Takahashi H, Suzuki H, Naiki H, Mizusawa H
    • Organizer
      PRION2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Possible transmission of cerebral β-amyloidosis via cadaveric dura mater graft2017

    • Author(s)
      Hamaguchi T, Yamada M
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Possible human-to-human transmission of cerebral β-amyloidosis via cadaveric dura mater grafting2017

    • Author(s)
      Yamada M, Hamaguchi T, Taniguchi Y, Sakai K, Kitamoto T, Takao M, Murayama S, Iwasaki Y, Yoshida M, Shimizu H, Kakita A, Takahashi H, Suzuki H, Naiki H, Sanjo N, Mizusawa H
    • Organizer
      Alzheimer's Association International Conference (AAIC) 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Book] Stroke Revisited: Pathophysiology of Stroke2020

    • Author(s)
      Yamada M, Sakai K, Hamaguchi T, Noguchi-Shinohara M
    • Total Pages
      291
    • Publisher
      Springer
    • ISBN
      9789811014291
    • Related Report
      2020 Annual Research Report
  • [Book] 今日の治療指針 2020年版2020

    • Author(s)
      山田正仁
    • Total Pages
      2192
    • Publisher
      医学書院
    • ISBN
      9784260039390
    • Related Report
      2020 Annual Research Report
  • [Book] 新臨床内科学  第10版2020

    • Author(s)
      山田正仁
    • Total Pages
      2002
    • Publisher
      医学書院
    • ISBN
      9784260038065
    • Related Report
      2020 Annual Research Report
  • [Book] 内科学書 改訂第9版 Vol.6 血液・造血器疾患2019

    • Author(s)
      山田正仁
    • Total Pages
      3672
    • Publisher
      中山書店
    • ISBN
      9784521747491
    • Related Report
      2019 Annual Research Report
  • [Book] アルツハイマー病 発症メカニズムと新規診断法・創薬・治療開発2018

    • Author(s)
      濵口 毅、山田正仁
    • Total Pages
      460
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2018 Annual Research Report
  • [Remarks] 金沢大学大学院 医薬保健学総合研究科 医学専攻 脳老化・神経病態学(脳神経内科学)

    • URL

      http://neurology.w3.kanazawa-u.ac.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 金沢大学大学院医薬保健学総合研究科 医学専攻 脳老化・神経病態学(脳神経内科学)ホームページ

    • URL

      http://neurology.w3.kanazawa-u.ac.jp

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 金沢大学大学院医薬保健学総合研究科神経内科 医学専攻 脳老化・神経病態学(神経内科学)ホームページ

    • URL

      http://neurology.w3.kanazawa-u.ac.jp

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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