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Study on biomarkers of Alzheimer's disease for personalized medicine

Research Project

Project/Area Number 26460200
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionNagasaki University

Principal Investigator

SHIROTANI Keiro  長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (20322696)

Co-Investigator(Kenkyū-buntansha) 大槻 純男  熊本大学, 大学院生命科学研究部(薬), 教授 (60323036)
Co-Investigator(Renkei-kenkyūsha) IWATA Nobuhisa  長崎大学, 医歯薬学総合研究科(薬学系), 教授 (70246213)
ARAI Hiroyuki  東北大学, 大学院医学研究科, 教授 (30261613)
URAKAMI Katsuya  鳥取大学, 医学部, 教授 (30213507)
HASHIMOTO Yasuhiro  福島県立医科大学, 医学部, 教授 (80164797)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsアルツハイマー病 / バイオマーカー / iPS細胞 / プロテオミクス / 質量分析 / LC-MSMS / レクチン / アミロイドベータ / アミロイド / 脳脊髄液
Outline of Final Research Achievements

To identify the subtype-specific biomarkers of Alzheimer’s disease (AD), iPS cells, which are derived from AD patients who showed accumulation of amyloid beta peptide inside or outside of neurons (intracellular and extracellular AD subtype, respectively), were differentiated into neurons and the culture media were purified and analyzed by liquid chromatography-tandem mass spectrometry (LC-MSMS) for comprehensive and quantitative analysis. We selected several biomarker candidates for intracellular, extracellular and common AD . We next quantitated the levels of the candidates in the culture media by multiplexed-MRM (multiple reaction monitoring) method and have confirmed three candidates show the same change as analyzed by LC-MSMS.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2017 2016 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Paradigm shift from diagnosing patients based on common symptoms to categorizing patients into subtypes with different pathogenic mechanisms to guide treatment for Alzheimer’s disease2017

    • Author(s)
      Shirotani K, Asai M, and Iwata N
    • Journal Title

      J Biochemistry

      Volume: 印刷中 Pages: 463-470

    • DOI

      10.1093/jb/mvx015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts2017

    • Author(s)
      Kawakubo T, Mori R, Shirotani K, Iwata N, and Asai M
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 3 Pages: 327-333

    • DOI

      10.1248/bpb.b16-00825

    • NAID

      130005398491

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Perturbed calcineurin-NFAT signaling is associated with the development of Alzheimer's disease2016

    • Author(s)
      Asai M, Kinjo A, Kimura S, Mori R, Kawakubo T, Shirotani K, Yagishita S, Maruyama K, and Iwata N
    • Journal Title

      Biol Pharm Bull

      Volume: 39 Pages: 1646-1652

    • NAID

      130005598494

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 患者由来iPS細胞を利用したアルツハイマー病のサブタイプ特異的バイオマーカーの探索2017

    • Author(s)
      岩田 修永、松尾 和哉、大槻 純男、浅井 将、近藤 孝之、井上 治久、城谷 圭朗
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      ブリックホール(長崎県・長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Study on signal transduction from microglial receptor TREM2, a new risk factor of Alzheimer's disease2017

    • Author(s)
      Shirotani K, Higuchi E, Yoshizaki R, Matsuo K, Asai M, Saito T, and Iwata N
    • Organizer
      The 19th Takeda Science Foundation Symposium on Bioscience
    • Place of Presentation
      Center for Learning and Innovation, Takeda Pharmaceutical Company, Ltd (CLI) (大阪府大阪市)
    • Year and Date
      2017-01-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アルツハイマー病サブグループのバイオマーカーの探索2016

    • Author(s)
      松尾 和哉、大槻 純男、浅井 将、城谷 圭朗、近藤 孝之、井上 治久、岩田 修永
    • Organizer
      第33回日本薬学会九州支部大会
    • Place of Presentation
      鹿児島大学(鹿児島県・鹿児島市)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 患者由来iPS細胞を利用したアルツハイマー病のバイオマーカーの探索2016

    • Author(s)
      岩田 修永、松尾 和哉、大槻 純男、浅井 将、近藤 孝之、井上 治久、城谷 圭朗
    • Organizer
      第35回日本認知症学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] アルツハイマー病サブグループのバイオマーカーの探索2016

    • Author(s)
      松尾 和哉、吉崎 涼平、大槻 純男、浅井 将、城谷 圭朗、近藤 孝之、井上 治久、岩田 修永
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センタ―他(宮城県・仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of biomarkers specific for Alzheimer's disease subgroups2016

    • Author(s)
      Matsuo K, Ohtsuki S, Asai M, Shirotani K, Kondo T, Inoue H, and Iwata N
    • Organizer
      The 8th Takeda Science Foundation Symposium on PharmaSciences
    • Place of Presentation
      武田薬品研修所(大阪府・吹田市)
    • Year and Date
      2016-01-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 疾患iPS細胞を用いたアルツハイマー病サブタイプ特異的バイオマーカーの探索2015

    • Author(s)
      松尾 和哉、大槻 純男、浅井 将、城谷 圭朗、近藤 孝之、井上 治久、岩田 修永
    • Organizer
      平成27年度日本生化学会九州支部例会
    • Place of Presentation
      九州大学箱崎キャンパス(福岡県・福岡市)
    • Year and Date
      2015-05-16
    • Related Report
      2015 Research-status Report
  • [Presentation] 患者iPS細胞由来神経細胞を用いたアルツハイマー病の病態解析 -Aβ蓄積とオートファジーの機能破綻-2015

    • Author(s)
      岩田 修永、森田 知樹、小出 恵理子、渡辺 かおり、近藤 孝之、井上 治久、浅井 将、城谷 圭朗
    • Organizer
      JST-再生医療実現拠点ネットワークプログラム [疾患特異的iPS細胞を活用した難病研究]・JST-CREST[iPS細胞領域]合同シンポジウム
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2015-02-23
    • Related Report
      2014 Research-status Report
  • [Presentation] Autophagy dysfunction in the neuronal cells derived from Alzheimer's disease patients2015

    • Author(s)
      Morita T, Koide E, Watanabe K, Kondo T, Asai M, Shirotani K, Inoue H, Iwata N
    • Organizer
      The 18th Takeda Science Foundation Symposium on Bioscience
    • Place of Presentation
      武田薬品研修所(大阪府吹田市)
    • Year and Date
      2015-01-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] アルツハイマー病iPS細胞由来神経細胞のオートファジー関連分子の解析2014

    • Author(s)
      城谷 圭朗、能登 雄太、髙橋 茜、森田 知樹、小出 恵理子、浅井 将、近藤 孝之、井上 治久、岩田 修永
    • Organizer
      第33回日本認知症学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-11-29 – 2014-12-01
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] iPS細胞を駆使した認知症のグライコバイオロジー2014

    • Author(s)
      城谷 圭朗
    • Organizer
      第33回日本糖質学会年会
    • Place of Presentation
      名古屋大学豊田講堂(愛知県名古屋市)
    • Year and Date
      2014-08-10 – 2014-08-14
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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