Physiological function of Aβ in regulation of brain cholesterol

2011 Fiscal Year Final Research Report

• 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
• Keywords: コレステロール / Aβ / アルツハイマー病

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 Aβ oligomers resulting in memory impairment in Alzheimer's disease model mice (2012)
  • Author(s): Umeda T., Tomiyama T., Kitajima E., Idomoto T., Nomura S., Lambert M. P., Klein W. L., Mori H
  • Journal Title: Life Sci Volume: (in press) Pages: 90
  • DOI: doi:10.1016/j.lfs.2011.12.022
  • 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
• [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
  • Year and Date: 20111112-16
• [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
  • Year and Date: 20111111-13
• [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
  • Year and Date: 20100710-15
• [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
  • Year and Date: 20100710-15
• [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
  • Year and Date: 20091120-22