29 November 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.
Reference:Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G.
Decreased prevalence of Alzheimer's disease associated with 3-hydroxy-3-methyglutaryl
coenzyme A reductase inhibitors. Arch Neurol 2000 Oct;57(10):1439-43 Abstract
Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, Duff K, Pappolla MA.
Hypercholesterolemia accelerates the Alzheimer's amyloid pathology
in a transgenic mouse model. Neurobiol Dis 2000 Aug;7(4):321-31. Abstract