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2020 Fiscal Year Annual Research Report

Study of Hirosaki Family with dominantly inherited Alzheimer's disease

Research Project

Project/Area Number 18K07385
Research InstitutionGunma University

Principal Investigator

東海林 幹夫  群馬大学, 医学部, 非常勤講師 (60171021)

Project Period (FY) 2018-04-01 – 2021-03-31
Keywords常染色体優性遺伝性アルツハイマー病 / バイオマーカー / 脳脊髄液 / 血液 / Abeta / リン酸化タウ
Outline of Annual Research Achievements

本研究では優性遺伝性アルツハイマー病(DIAD)家系とこれまでに収集した孤発例アルツハイマー病者と国際的な共同研究により、アルツハイマー病の 1)臨床経過,2)最新の認知機能検査と3)バイオマーカーの自然経過を明らかにできた.これらの研究は,1)アミロイドアンギオパチ-による微小出血はMCI段階から急激に増加する(Neurology).2)新たに開発した質量分析による測定でAbeta42と43がCSFで低下すること(J Alzheimer Dis).3)CogEVOなどの新たな認知機能検査を開発し、アルツハイマー病における無症候期の認知機能の評価システムを開発したこと(Geriat Geronto Int).4)CSFのリン酸化タウのうちp217およびp181がMCI段階よりも20年以上前から増加する事 (Nature Med),5)血液リン酸化タウ測定を目指して,新たなタウな測定系を開発したこと (Neurosci Lett),6)ライフスタイルによる脳アミロイドやタウ病理の変化を明らかにしたこと(Biol Psych)、6)APOE遺伝型と血液Abeta40,42,認知機能,他の血液バイオマーカーとの相関(Ann Clin Trans Neurol) 等の成果として論文発表された.さらに,初年度のCSFやplasmaにおけるAbeta,タウ, リン酸化タウ,アルファシヌクレインの測定報告(J Alzheimer Dis)や血液Neurofilament light chainがMCI段階より.6.8年前から増加してくる報告(Nature Med)と合わせると,遺伝性・家族性アルツハイマー病の自然経過を明らかにして,今後の臨床診断や根本的治療法の開発に,大きな貢献ができたものと考えられる.

  • Research Products

    (14 results)

All 2021 2020 Other

All Int'l Joint Research (5 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Washington University/Mayo Clinic/Harvard Medical School(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      Washington University/Mayo Clinic/Harvard Medical School
    • # of Other Institutions
      18
  • [Int'l Joint Research] DZNE center/Tubigen University/Ludwig-Maximillians-University(ドイツ)

    • Country Name
      GERMANY
    • Counterpart Institution
      DZNE center/Tubigen University/Ludwig-Maximillians-University
    • # of Other Institutions
      2
  • [Int'l Joint Research] FLEN Institute(アルゼンチン)

    • Country Name
      ARGENTINA
    • Counterpart Institution
      FLEN Institute
  • [Int'l Joint Research] Melborne University/Edith Cowan University/Macquarie University(オーストラリア)

    • Country Name
      AUSTRALIA
    • Counterpart Institution
      Melborne University/Edith Cowan University/Macquarie University
    • # of Other Institutions
      4
  • [Int'l Joint Research] Queens Square Institute/London University(英国)

    • Country Name
      UNITED KINGDOM
    • Counterpart Institution
      Queens Square Institute/London University
  • [Journal Article] Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease2021

    • Author(s)
      Joseph-Mathurin Nelly、Wang Guoqiao、Kantarci Kejal、Jack Clifford R.、McDade Eric、et al
    • Journal Title

      Neurology

      Volume: 96 Pages: e1632~e1645

    • DOI

      10.1212/WNL.0000000000011542

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative Measurement of Cerebrospinal Fluid Amyloid-β Species by Mass Spectrometry2021

    • Author(s)
      Seino Yusuke、Nakamura Takumi、Harada Tomoo、Nakahata Naoko、Kawarabayashi Takeshi、Ueda Tetsuya、Takatama Masamitsu、Shoji Mikio
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 79 Pages: 573~584

    • DOI

      10.3233/JAD-200987

    • Peer Reviewed / Open Access
  • [Journal Article] Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer’s Disease2021

    • Author(s)
      Pichet Binette Alexa、Vachon-Presseau E、Morris John、Bateman Randall、et al
    • Journal Title

      Biological Psychiatry

      Volume: 89 Pages: 776~785

    • DOI

      10.1016/j.biopsych.2020.01.023

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An autopsy case of primary lateral sclerosis with Alzheimer's disease2020

    • Author(s)
      Nakamura Takumi、Kon Tomoya、Kawarabayashi Takeshi、Wakabayashi Koichi、Ikeda Yoshio、Shoji Mikio
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 412 Pages: 116792~116792

    • DOI

      10.1016/j.jns.2020.116792

    • Peer Reviewed
  • [Journal Article] A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease2020

    • Author(s)
      Barthelemy Nicolas R.、the Dominantly Inherited Alzheimer Network、et al
    • Journal Title

      Nature Medicine

      Volume: 26 Pages: 398~407

    • DOI

      10.1038/s41591-020-0781-z

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel ELISAs to measure total and phosphorylated tau in cerebrospinal fluid2020

    • Author(s)
      Kawarabayashi Takeshi、Nakamura Takumi、Miyashita Kazuya、Fukamachi Isamu、Seino Yusuke、Shoji Mikio
    • Journal Title

      Neuroscience Letters

      Volume: 722 Pages: 134826~134826

    • DOI

      10.1016/j.neulet.2020.134826

    • Peer Reviewed
  • [Journal Article] A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology2020

    • Author(s)
      Abe Koji、Shang Jingwei、Shi Xiaowen、Yamashita Toru、et al
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 73 Pages: 217~227

    • DOI

      10.3233/JAD-191016

    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Cerebrospinal fluid and plasma biomarkers in neurodegenerative diseases2020

    • Author(s)
      Kawarabayashi T, Seino Y, Nakamura T, Takatama M, Shoji M
    • Organizer
      61st annual meeting of Japanese society of Neurology
    • Int'l Joint Research
  • [Presentation] Oral immunization with soybean storage protein containing amyloid Abeta 4-10 prevents spatial learning decline2020

    • Author(s)
      Takeshi Kawarabayashi, Takumi Nakamura, Yusuke Seino, Masamitsu Takatama, Mikio Shoji
    • Organizer
      Alzheimer’s Association International Conference (AAIC) 2020
    • Int'l Joint Research

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Published: 2021-12-27  

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