ACAT as a drug target for Alzheimer's disease

Abstract

Accumulation of β-amyloid peptide (Aβ) in the brain regions responsible for memory and cognitive functions is a neuropathological hallmark of Alzheimer's disease. Cholesterol may be involved in many aspects of Aβmetabolism. It affects generation, aggregation and clearance of Aβin the brain. Not only the amount but also the distribution of cholesterol within cells appears to modulate Aβbiogenesis. ACAT is an enzyme that regulates subcellular cholesterol distribution by converting membrane cholesterol to cholesteryl esters for storage and transport. We have used various cell- and animal based models to show that inhibition of ACAT strongly reduces Aβgeneration and protects from amyloid pathology. Here, we discuss data supporting ACAT inhibition as a strategy to treat Alzheimer's disease. Copyright © 2008 S. Karger AG.