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2003 Fiscal Year Final Research Report Summary

Influence of membrane lipid metabolism on cerebral amyloid deposition and neurodegeneration.

Research Project

Project/Area Number 13480250
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionGunma University

Principal Investigator

YAMAGUCHI Haruyasu  Gunma University, School of Health Sciences, Professor, 医学部, 教授 (00158114)

Co-Investigator(Kenkyū-buntansha) SASAKI Atsushi  Gunma University, School of Medicine, Assistant Professor, 医学部, 講師 (80225862)
YANAGISAWA Katsuhiko  National Institute for Longevity Science, Director, 痴呆疾患研究部, 部長 (10230260)
C.FUJITA Shinobu  Mitsubishi Kasei Life Science Institute, Senior Researcher, 生命科学研究所, 主任研究員
Project Period (FY) 2001 – 2003
KeywordsAlzheimer's disease / amyloid / dementia / ApoE / animal model / raft
Research Abstract

We examined the ultrastructure of rafts in rat brain tissue by pre-embedding immunoelectron microscopy using flotillin-1 antibody, which is biochemical marker of lipid rafts, and BCθ, which is nicked and biotinylated θ-toxin, and binds to membrane cholesterol of rafts. Flotillin-1-and BCθ-labeled areas were patchy and prominent on the plasma membranes of small processes and synapses in the neuropil. The size of flotillin-1 labeling was 40 to 200nm.In addition, the membrane of lysosome and Golgi apparatus were frequently labeled for flotillin-1 with a patchy pattern. Flotillin-1 and BCθ were mostly colocalized in double immunolabeling on a part of the plasma membranes of small processes and secondary lysosome membranes. We first indicate that flotillin-1 localizes to BCθ-positive cholesterol-rich membrane microdomains in vivo, and that flotillin-1 and BCθ could be an ultrastructural rafts marker in neural tissue. We also examined the relation between lipid raft and cerebral β-amyloid deposition in the Tg2576 transgenic mouse.
Moreover, we found a striking difference in the distribution of membrane cholesterol. ApoE4 knock-in mice showed an approximately 2-fold increase in exofacial leaflet cholesterol compared with apoE3 knock-in mice and wild-type mice.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Yamaguchi H: "Alzheimer β amyloid deposition enhanced by ApoE ε4 gene, precedes neurofibrillary pathology in the frontal association cortex of non-demented senior subjects."J Neuropathol Exp Neurol. 60. 731-739 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kokubo H: "Ultrastructural localization of flotillin-1 to cholesterol-rich membrane microdomains, rafts, in rat brain tissue"Brain Res. 965. 83-90 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sai X: "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid β-protein"J Biol Chem. 277. 12915-12920 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori T: "Increased vulnerability to focal ischemic brain injury in human apolippoprotein E4 knock-in mice"J.Neuropathol.Exp.Neurol. 62. 280-291 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi H: "Choleterol is increased in the expfacial leaflet of synaptic plasma membranes of human apolipoprotein E4 knock-in mice"NeuroReport. 13. 383-386 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi RH: "Intraneuronal Alzneimer Abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology"Am J Pathol. 161. 1869-1879 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaguchi H: "Alzheimer β amyloid deposition enhanced by ApoE ε4 gene, precedes neurofibrillary pathology in the frontal association cortex of non-demented senior subjects."J Neuropathol Exp Neurol. 60. 731-739 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi RH: "Intraneuronal Alzheimer Aβ42 accumulates in multivesicular bodies and is associated with synaptic pathology."Am J Pathol. 161. 1869-1879 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kokubo H: "Ultrastructural localization of flotillin-1 to cholesterol-rich membrane microdomains, rafts, in rat brain tissue."Brain Res. 965. 83-90 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sai X: "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid β-protein."J Biol Chem. 277. 12915-12920 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori T: "Increased vulnerability to focal ischemic brain injury in human apolippoprotein E4 knock-in mice."J.Neuropathol.Exp.Neurol.. 62. 280-291 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi H: "Cholesterol is increased in the exofacial leaflet of synaptic plasma membranes of human apolipoprotein E4 knock-in mice."NeuroReport. 13. 383-386 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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