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

Luigi Puglielli, Genevieve Konopka, Eunju Pack-Chung, Laura A MacKenzie Ingano, Oksana Berezovska, Bradley T. Hyman, Ta Yuan Chang, Rudolph E. Tanzi, Dora M. Kovacs

Research output: Contribution to journalArticlepeer-review

396 Scopus citations


The pathogenic event common to all forms of Alzheimer's disease is the abnormal accumulation of the amyloid β-peptide (Aβ). Here we provide strong evidence that intracellular cholesterol compartmentation modulates the generation of Aβ. Using genetic, biochemical and metabolic approaches, we found that cholesteryl-ester levels are directly correlated with Aβ production. Acyl-coenzyme A:cholesterol acyltransferase (ACAT), the enzyme that catalyses the formation of cholesteryl esters, modulates the generation of Aβ 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 Aβ generation, indicating their potential for use in the treatment of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)905-912
Number of pages8
JournalNature cell biology
Issue number10
StatePublished - 2001

ASJC Scopus subject areas

  • Cell Biology


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