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Novel quantitative analysis of abnormal phosphorylated tau

Research Project

Project/Area Number 15K18366
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionTokyo Metropolitan University

Principal Investigator

KIMURA TAEKO  首都大学東京, 理工学研究科, 特任研究員 (60748820)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsタウ / リン酸化 / Phos-Tag SDS-PAGE法 / Cdk5 / ヒト患者脳 / タウオパチー / タウアイソフォーム / R406W / アルツハイマー病 / Tau / ADモデルマウス / 患者脳
Outline of Final Research Achievements

Tau is hyperphosphorylated in the brains of patients with tauopathies, such as Alzheimer's disease. However, neither the mechanism of hyperphosphorylation nor its contribution to pathogenesis is known. I applied the Phos-tag SDS-PAGE. Here, I found ~12 phosphorylation isotypes of tau in culture cells with different combinations of phosphorylation at Thr181, Ser202, Thr231, Ser235 and Ser404. These phosphorylation sites were similar to tau phosphorylated in mouse brains. In normal elderly human brains, nonphosphorylated 0N3R and 0N4R tau were most abundant. A slightly higher phosphorylation of tau, which may represent the early step of hyperphosphorylation, was increased in Alzheimer disease patients at Braak stage V. Tau was pelleted by centrifugation, and sarkosyl-soluble tau in either Alzheimer disease or corticobasal degeneration brains showed phosphorylation profiles similar to tau in normal human brain, suggesting that hyperphosphorylation occurs in aggregated tau.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2016 2015

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Quantitative and combinatory determination of in situ phosphorylation of tau and its FTDP-17 mutants.2016

    • Author(s)
      Kimura T, Hosokawa T, Taoka M, Tsutsumi K, Ando K, Ishiguro K, Hosokawa M, Hasegawa M, Hisanaga S.
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 33479-33479

    • DOI

      10.1038/srep33479

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Abundance of Nonphosphorylated Tau in Mouse and Human Tauopathy Brains Revealed by the Use of Phos-Tag Method.2016

    • Author(s)
      Kimura T, Hatsuta H, Masuda-Suzukake M, Hosokawa M, Ishiguro K, Akiyama H, Murayama S, Hasegawa M, Hisanaga S.
    • Journal Title

      Am J Pathol

      Volume: 186 Pages: 398-409

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Tauは細胞内で多様なリン酸化状態として存在する2016

    • Author(s)
      木村妙子、石黒幸一、 長谷川成人、 久永眞市
    • Organizer
      第59回 日本神経化学会
    • Place of Presentation
      福岡
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Tauは細胞内で多様なリン酸化状態として存在する2016

    • Author(s)
      木村妙子、久永眞市
    • Organizer
      第4回新学術班会議
    • Place of Presentation
      千葉
    • Year and Date
      2016-06-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] The abundance of nonphosphorylated tau among heterogeneously phosphorylated tau species in vivo in mouse and human tauopathy brains2015

    • Author(s)
      Taeko Kimura
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      埼玉
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Phos-tag SDS-PAGE法による神経変性疾患タウのリン酸化解析2015

    • Author(s)
      木村妙子
    • Organizer
      第66回電気泳動学会
    • Place of Presentation
      東京
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] New insights in quantitative analysis of phosphorylation of Tau in AD model mouse and Tauopathy brains by Phos-tag SDS-PAGE.2015

    • Author(s)
      Taeko Kimura
    • Organizer
      25th meeting of the International society for neurochemistry
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      2015-08-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-03-22  

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