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2002 Fiscal Year Final Research Report Summary

Cholesterol metabolism and Amyloid βprotein synthesis : Attention to Niemann-Pick discase type C

Research Project

Project/Area Number 13670632
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionGunma University (2002)
The University of Tokyo (2001)

Principal Investigator

YAMAZAKI Tsuneo  Gunma University, Medicine, Assist. Prof, 医学部, 講師 (80200658)

Project Period (FY) 2001 – 2002
KeywordsAlzheimer's disease / Cholesterol / Niemann-Pick disease / Amyloid βprotein
Research Abstract

Amyloid β protein (Aβ) is a component of senile plaques, which are characteristic brain structures of Alzheimer's disease, and a putative causal molecule of the disease. Although the precise intracellular site of Aβ production is not known, cholesterol depletion strongly decreases the Aβ production in cultured cells. To investigate whether disturbance of intracellular cholesterol trafficking also affects the Aβ generation, we treated cultured cells with a compound which affects the cholesterol transport in late endosomes / lysosomes. These treatments caused cells to significantly accumulate Aβ, especially Aβ42 species, inside the cells. This accumulated Aβ was SDS insoluble but formic acid soluble, thus presumably an aggregated form. Cell fractionation studies revealed that the Aβ accumulated in the same fractions as free cholesterol. These results may indicate a strong interaction between free cholesterol and Aβ42 within the cell, and suggests that this particular metabolic pathway is responsible for intracellular accumulation of Aβ.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Yamazaki, T., Chang, T.-Y., Haass, C., Ihara, Y.: "Accumulation and aggregation of amyloid β-protein in late endosomes of Niemann-Pick type C cells"J. Biol. Chem.. 276. 4454-4460 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山崎恆夫, 井原康夫: "アルツハイマー病における神経細胞死"実験医学. 19. 1768-1771 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山崎恆夫, 岡本幸市: "コレステロールはAlzheimer病の発症に関与しているか?"Current insights in Neurological Science. 10. 10-11 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamazaki, T., Chang, T. -Y., Haass, C., Ihara, Y.: "Accumulation and aggregation of amyloid β-protein in late end osomes of Niemann-Pick type C cells"J. Biol. Chem.. 276. 4454-4460 (2001)

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

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Published: 2004-04-14  

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