Physiological function of Aβ in regulation of brain cholesterol

• Project/Area Number: 21500352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Osaka City University
• Principal Investigator: TOMIYAMA Takami 大阪市立大学, 大学院・医学研究科, 准教授 (10305633)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: コレステロール / Aβ / アルツハイマー病 / HDL / ABCA1 / アポリポ蛋白質 / 危険因子

Research Abstract

In this study, we found a novel, apolipoprotein-like function of Aβthat mediates cholesterol efflux from cells in cooperation with the membrane cholesterol transporter ABCA1.Aβwas also shown to promote cholesterol transport from the brain into the liver. These findings imply the biological significance of cholesterol-induced Aβproduction and explain why high levels of plasma cholesterol are a risk factor for Alzheimer's disease.

Research Products

• [Journal Article] Hypercholesterolemia accelerates intraneuronal accumulation of Aboligomers resulting in memory impairment in Alzheimer's disease model mice (2012)
  • Author(s): Umeda T, Tomiyama T, KitajimaE, Idomoto T, Nomura S, Lambert M.P, Klein W.L, Mori H
  • Journal Title: Life Science Volume: 90(in Press) Issue: 23-24 Pages: 90-90
  • DOI: 10.1016/j.lfs.2011.12.022
  • Peer Reviewed
• [Journal Article] 高コレステロール血症は脳のAβオリゴマーを増加させることでトランスジェニックマウスの記憶障害を加速する (2011)
  • Author(s): 北島えりか
  • Journal Title: 大阪市医学会雑誌 Volume: 60(In press)
  • Peer Reviewed
• [Journal Article] Regulation of cholesterol efflux by amyloidβsecretion (2010)
  • Author(s): Umeda T., Mori H., Zheng H., Tomiyama T
  • Journal Title: J. Neurosci. Res. Volume: 88 Pages: 1985-1994
  • Peer Reviewed
• [Journal Article] Regulation of cholesterol efflux by amyloid β secretion (2010)
  • Author(s): Tomohiro Umeda
  • Journal Title: Jourmal of Neuroscience Research Volume: 88 Pages: 1985-1994
  • Peer Reviewed
• [Presentation] The E693Δmutation in amyloid precursor protein impairs Aβ-mediated cholesterol efflux from cells (2011)
  • Author(s): Nomura S, Umeda T, Tomiyama T, Lambert MP, Klein WL, Mori H
  • Organizer: 41st Annual Meeting of Society for Neuroscience
  • Place of Presentation: Washington, DC, USA
• [Presentation] The E693Δmutation in amyloid precursor protein impairs Aβ-mediated cholesterol efflux from cells in vitro (2011)
  • Author(s): 梅田知宙、野村幸子、富山貴美、森啓
  • Organizer: 第30回日本認知症学会
  • Place of Presentation: 東京
• [Presentation] The E693Δ mutation in amyloid precursor protein impairs Aβ-mediated cholesterol efflux from cells, leading to accelerated accumulation of intraneuronal Aβ oligomers and memory disturbance in mice with hypercholesterolemia (2011)
  • Author(s): Nomura S, Umeda T, Tomiyama T, Lambert MP, Klein WL, Mori H
  • Organizer: 41st Annual Meeting of Society for Neuroscience
  • Place of Presentation: Washington, DC, USA
• [Presentation] The E693Δ mutation in amyloid precursor protein impairs Ass-mediated cholesterol efflux from cells in vitro (2011)
  • Author(s): 梅田知宙、野村幸子、富山貴美、森啓
  • Organizer: 第30回日本認知症学会
  • Place of Presentation: 東京
• [Presentation] Hypercholesterolemia accelerates memory impairment in a transgenic mouse model of Aβ Oligomers. (2010)
  • Author(s): Erika Kitajima
  • Organizer: International Conference on Alzheimer's Disease(ICAD)2010
  • Place of Presentation: 米国ホノルル、ハワイコンベンションセンター
  • Year and Date: 2010-07-11
• [Presentation] Regulation of cholesterol efflux by amyloidβ secretion (2010)
  • Author(s): Umeda T, Mori H, Zheng H, Tomiyama T
  • Organizer: International Conference on Alzheimer's disease(ICAD) 2010
  • Place of Presentation: Honolulu, USA
• [Presentation] Hypercholesterolemia accelerates memory impairment in a transgenic mouse model of Aβ oligomers (2010)
  • Author(s): Kitajima E, Umeda T, Idomoto T, Lambert MP, Klein WL, Tomiyama T, Mori H
  • Organizer: International Conference on Alzheimer's disease(ICAD) 2010
  • Place of Presentation: Honolulu, USA
• [Presentation] Aβ分泌によるコレステロールeffluxの制御 (2009)
  • Author(s): 梅田知宙
  • Organizer: 日本認知症学会
  • Place of Presentation: 東北大学百周年記念館(仙台市)
  • Year and Date: 2009-11-20
• [Presentation] Aβ分泌によるコレステロールeffluxの制御 (2009)
  • Author(s): 梅田知宙、森啓、Zheng Hui、富山貴美
  • Organizer: 第29回日本認知症学会
  • Place of Presentation: 仙台