Identification of molecules related to modulation of Amyloid beta production in human cerebrospinal fluid (CSF)

• Project/Area Number: 25461766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: Takashi Kodama 大阪大学, 医学(系)研究科(研究院), 特任研究員(常勤) (30512131)
• Co-Investigator(Kenkyū-buntansha): OKOCHI Masayasu 大阪大学, 医学研究科, 講師 (90335357) ; TAGAMI Shinji 大阪大学, 医学研究科, 助教 (40362735) ; YANAGIDA Kanta 大阪大学, 医学研究科, 特任研究員 (70467596)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アルツハイマー病 / 質量分析 / アミロイドベータ産生機構 / APL1ベータペプチド / バイオマーカー / 神経変性疾患 / 脳脊髄液

Outline of Final Research Achievements

In this study, molecules in human cerebrospinal fluid (CSF) have been investigated using LC/MS/MS measurements and amino acid sequence search using public and home-developed databases. The purpose of this study is to establish a method to identify and quantify peptides which is related to the modulation of gamma-secretase and beta-secretase activities in Alzheimer’s disease (AD). We have identified 102 of membrane proteins, 54 of disease associated proteins, and 2 of neuro degeneration-related proteins in human CSF. We also developed and improved an advanced liquid chromatography tandem mass spectrometry (LC/MS/MS) method to determine the concentration of sub-femtomolar order of APLP1 derived peptides which is an established molecular marker of AD.

Research Products

• [Presentation] ヒト血漿中に存在するAβペプチドのサロゲートマーカーAPL1βのLC-MS/MSによる測定 (2015)
  • Author(s): 児玉高志、大河内正康、田上真次、柳田寛太、森原剛史、田中稔久、工藤喬、朝長毅、武田雅俊
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: リンクステーション青森
  • Year and Date: 2015-10-02
• [Presentation] 細胞内に存在するAbeta由来のオリゴペプチドのLC-MS/MSによる測定 (2014)
  • Author(s): 児玉高志、大河内正康、田上真次、柳田寛太、水田直樹、高見真子、井原康夫、武田雅俊
  • 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 会議センター
  • Year and Date: 2014-11-29 – 2014-12-01
• [Presentation] アミロイドベータ産生機構解析のための細胞内ペプチドの測定 (2014)
  • Author(s): 児玉高志、大河内正康、田上真次、柳田寛太、高見真子、井原康夫、武田雅俊
  • Organizer: 第25回日本老年医学会近畿地方会
  • Place of Presentation: 和歌山県立医科大学
  • Year and Date: 2014-10-11
• [Presentation] Identification and quantitative analysis of short peptides derived from amyloid-beta peptides in living cell
  • Author(s): Kodama T.S., Okochi M., Tagami S., Yanagida K., Mizuta N., Tanaka T., Morihara T., Kudo T., Takami M., Ihara Y., Takeda M.
  • Organizer: IPA’s 16th International Congress
  • Place of Presentation: COEX( Seoul Korea)