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

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