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Transmission study of Alzheimer pathology using brain microdialysis

Research Project

Project/Area Number 24659434
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionOsaka City University

Principal Investigator

TOMIYAMA Takami  大阪市立大学, 医学(系)研究科(研究院), 准教授 (10305633)

Co-Investigator(Kenkyū-buntansha) UMEDA Tomohiro  大阪市立大学, 医学研究科, 助教 (70549790)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsマイクロダイアリシス / アルツハイマー病 / トランスジェニックマウス / Aβ / タウ / アミロイドβ / 病理伝播
Research Abstract

The purpose of this study is to examine the possible roles of soluble Abeta and tau released from neurons into the extracellular space in the transmission of Alzheimer pathology using the brain microdialysis technique. In a preliminary experiment, only very low levels of tau were detected by microdialysis in the hippocampus of our tau transgenic (Tg) mice. To generate a better donor of soluble Abeta and tau, we crossbred our APP Osaka mutant Tg mice and wild-type tau Tg mice. The resultant double Tg mice showed Abeta oligomer accumulation, tau hyperphosphorylation, synapse loss, and memory impairment at 6 months, and neurofibrillary tangle formation and neuronal loss at 18 months in the absence of tau mutations, all of which appeared earlier than in the parent Tg mice. This mouse model would be a useful tool for investigation of the intercellular propagation of amyloid and tau pathologies.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (13 results)

All 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 3 results) Presentation (5 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Neurofibrillary tangle formation by introducing wild-type human tau into APP transgenic mice2014

    • Author(s)
      Umeda T, Maekawa S, Kimura T, Takashima A, Tomiyama T, Mori H.
    • Journal Title

      Acta Neuropathol

      Volume: 127 Pages: 684-698

    • Related Report
      2013 Final Research Report
  • [Journal Article] Neurofibrillary tangle formation by introducing wild-type human tau into APP transgenic mice.2014

    • Author(s)
      Umeda T, Maekawa S, Kimura T, Takashima A, Tomiyama T, Mori H.
    • Journal Title

      Acta Neuropathol.

      Volume: 127(5) Issue: 5 Pages: 685-98

    • DOI

      10.1007/s00401-014-1259-1

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurodegenerative disorder FTDP-17 related tau intron 10 +16C→T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice2013

    • Author(s)
      Umeda T, Yamashita T, Kimura T, Ohnishi K, Takuma H, Ozeki T, Takashima A, Tomiyama T, Mori H.
    • Journal Title

      Am J Pathol

      Volume: 183 Pages: 211-225

    • Related Report
      2013 Final Research Report
  • [Journal Article] Neurodegenerative disorder FTDP-17-related tau intron 10 +16C → T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice.2013

    • Author(s)
      Umeda T, Yamashita T, Kimura T, Ohnishi K, Takuma H, Ozeki T, Takashima A, Tomiyama T, Mori H.
    • Journal Title

      Am J Pathol.

      Volume: 183(1) Issue: 1 Pages: 211-25

    • DOI

      10.1016/j.ajpath.2013.03.015

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurodegenerative disorder FTDP-17 related tau intron 10 +16C→T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice2013

    • Author(s)
      Umeda T, Yamashita T, Kimura T, Ohnishi K, Takuma H, Ozeki T, Takashima A, Tomiyama T, Mori H
    • Journal Title

      Am J Pathol

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 細胞内Aβオリゴマーによるアルツハイマー病発症機構2012

    • Author(s)
      富山貴美
    • Journal Title

      Dementia Japan

      Volume: 26 Pages: 225-241

    • Related Report
      2012 Research-status Report
  • [Journal Article] Aβオリゴマーを標的とするアルツハイマー病治療薬の展望2012

    • Author(s)
      富山貴美
    • Journal Title

      Dementia Japan

      Volume: 26 Pages: 300-310

    • Related Report
      2012 Research-status Report
  • [Presentation] FTDP-17 related tau intron 10 +16C→T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice2013

    • Author(s)
      Tomiyama T, Umeda T, Yamashita T, Ohnishi K, Takuma H, Mori H.
    • Organizer
      International Conference on Alzheimer's & Parkinson's Diseases (AD/PD2013)
    • Place of Presentation
      Florence, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] FTDP-17 related tau intron 10 +16C→T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice2013

    • Author(s)
      Tomiyama T, Umeda T, Yamashita T, Ohnishi K, Takuma H, Mori H
    • Organizer
      The 11th International Conference on Alzheimer’s & Parkinson’s Diseases (AD/PD2013)
    • Place of Presentation
      Firenze Fiera, Florence, Italy
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞内Aβオリゴマーによるシナプス障害と神経細胞死2012

    • Author(s)
      富山貴美
    • Organizer
      第31回日本認知症学会学
    • Place of Presentation
      つくば国際会議場、茨城県つくば市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Intron変異を有する新規FTDP-17モデルマウスの作製と解析2012

    • Author(s)
      梅田知宙、山下雄也、富山貴美、詫間浩、大西紀陽久、森啓
    • Organizer
      第31回日本認知症学会学
    • Place of Presentation
      つくば国際会議場、茨城県つくば市
    • Related Report
      2012 Research-status Report
  • [Presentation] Aβオリゴマーモデルマウスの解析とアルツハイマー病治療戦略2012

    • Author(s)
      富山貴美
    • Organizer
      Novartis NeuroScience Forum 2012
    • Place of Presentation
      グランドプリンスホテル新高輪、東京都港区
    • Related Report
      2012 Research-status Report
    • Invited
  • [Remarks] APPトランスジェニックマウスへの野生型ヒトタウの導入による神経原線維変化の形成

    • URL

      http://www.med.osaka-cu.ac.jp/Neurosci/news.html

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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