Cholesterol modulation as an emerging strategy for the treatment of Alzheimer's disease

The basis for therapeutic strategies targeting the amyloid-beta protein (Abeta) has come from studies showing that accumulation and aggregation of the Abeta within the brain is likely to cause Alzheimer's disease (AD). Along with an ever-increasing understanding of Abeta metabolism, many potential therapeutic strategies aimed at altering Abeta metabolism have emerged. Among the more intriguing targets for therapy are enzymes involved in cholesterol homeostasis, because it has been found that altering cholesterol can influence Abeta metabolism in experimental model systems, and that cholesterol-lowering agents, specifically HMG-CoA reductase inhibitors, could reduce the incidence of AD. It is likely that cholesterol influences Abeta metabolism in several ways, including altering Abeta production and perhaps altering Abeta deposition and clearance. Thus, pharmacological modulation of cholesterol levels could provide a relatively safe means to reduce Abeta accumulation in the brain, and thereby prevent or slow the development of AD.