29 Nov 2000

Statins have recently appeared on the radar screen for Alzheimer's researchers because of studies by Ben Wolozin and his colleagues showing that people who take the cholesterol-lowering drugs have a significantly reduced risk of Alzheimer's disease (see Wolozin, et al., Arch Neurol. 2000). The drugs reduce cholesterol levels by inhibiting the activity of a liver enzyme called 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and Konrad Beyreuther has proposed that reductions in cholesterol can alter APP metabolism so as to reduce production of A-β. New findings suggest that statins have other potent biologic effects, which might also account for the reported reduction in AD risk. A team led by François Mach at University Hospital Geneva reports in the December issue of Nature Medicine that statins block the ability of a cytokine called interferon-γ (IFNγ) to activate T cells. Normally, IFN-γ causes T cells to express the major histocompatibility complex class II (MHC-II) molecule that takes in foreign antigens and presents them on the surface of immune cells, thus propagating the inflammatory response. Comments Wolozin: "Our research suggests that statins might reduce the risk of Alzheimer's disease by a mechanism independent of the effects of statins on serum cholesterol. The actions of statins on the immune system could contribute to the protective effects of statins for AD, given the potential importance of inflammation in the pathophysiology of Alzheimer's disease. In addition, this work emphasizes that many of the beneficial effects of statins, such as the ability to reduce the risk of AD, could be independent of serum cholesterol."—June Kinoshita