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Selective Inhibition of ACAT1 Activity in the Treatment of Alzheimer’s Disease

Acyl-CoA:Cholesterol Acyltransferase (ACAT) converts free cholesterol to cholesterol ester, and is one of the key enzymes in cellular cholesterol metabolism. Two ACAT genes have been identified which encode two different enzymes, ACAT1 and ACAT2. While both ACAT1 and ACAT2 are present in the liver and intestine, the cells containing either enzyme within these tissues are distinct, suggesting that ACAT1 and ACAT2 have separate functions.

Dartmouth researchers have now found that ACAT1, but not ACAT2, plays a significant role in amyloid pathology of Alzheimer's disease in vivo. Specifically, ACAT1 modulates the sizes and densities of amyloid plaques and cognitive decline manifested in a mouse model for the Alzheimer's disease in vivo. Therefore, it is expected that inhibition of ACAT1 expression or activity with selective inhibitors such as small molecules or microRNAs can be used in the treatment of Alzheimer's disease.

This technology is claimed in the published PCT patent application No. PCT/US2009/056601. We are seeking an industrial partner interested in its commercialization. (Ref: J483)

Last Updated: 7/24/12