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Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid β-peptide

Puglielli, Luigi, Konopka, Genevieve, Pack-Chung, Eunju, Ingano, Laura A. MacKenzie, Berezovska, Oksana, Hyman, Bradley T., Chang, Ta Yuan, Tanzi, Rudolph E., Kovacs, Dora M.·2001·Nature Cell Biology
DOI 10.1038/ncb1001-905
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Abstract

The pathogenic event common to all forms of Alzheimer's disease is the abnormal accumulation of the amyloid beta-peptide (Abeta). Here we provide strong evidence that intracellular cholesterol compartmentation modulates the generation of Abeta. Using genetic, biochemical and metabolic approaches, we found that cholesteryl-ester levels are directly correlated with Abeta production. Acyl-coenzyme A:cholesterol acyltransferase (ACAT), the enzyme that catalyses the formation of cholesteryl esters, modulates the generation of Abeta through the tight control of the equilibrium between free cholesterol and cholesteryl esters. We also show that pharmacological inhibitors of ACAT, developed for the treatment of atherosclerosis, are potent modulators of Abeta generation, indicating their potential for use in the treatment of Alzheimer's disease.

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Metadata

Authors
Puglielli, L., Konopka, G., Pack-Chung, E., Ingano, L. A. M., Berezovska, O., Hyman, B. T., Chang, T. Y., Tanzi, R. E., & Kovacs, D. M.
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2001-09-17
Volume
3
Issue
10
Pages
905-912
ISSN
  • 1465-7392
  • 1476-4679
DOI
10.1038/ncb1001-905
Cited by
392
References
2
Language
en
Licence
www.springer.com/tdm (tdm)

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