Is ACAT a novel pharmacological target for the treatment of Alzheimer's disease?

Several independent epidemiological studies have suggested a role for cholesterol in the pathogenesis of Alzheimer's disease (Abeta). Consistent with this role, elevated cholesterol, levels have been reported to increase the biogenesis/deposition of amyloid beta-peptide (AD) in the brains of AD transgenic mouse models. Both cellular and biochemical studies have now confirmed the potential role of cholesterol metabolism and distribution in the regulation of the very first step of AD pathogenesis: the biogenesis of Abeta. Although the molecular mechanisms involved in the sterol-dependent regulation of AD generation have not yet been completely,, revealed, recent reports seem to implicate AcylCoA:cholesterol acyltransferase (ACAT), a key enzyme in the regulation of intracellular cholesterol distribution.