Differential effects of lovastatin treatment on brain cholesterol levels in normal and ApoE-deficient mice

Growing evidence indicates that membrane cholesterol is involved in the dev elopment of Alzheimer's disease. Therefore, the availability of pharmacolog ical strategies to modify brain cholesterol is of increasing importance. Ac cordingly, we investigated the effects of the HMG-CoA reductase inhibitor l ovastatin on brain cholesterol levels in vivo. Brain cholesterol was signif icantly decreased by lovastatin treatment (100 mg/kg/day) in 1- and 12-mont h-old C57BL/6J mice. Reduced brain cholesterol was associated with decrease d pyrene-excimer fluorescence, indicating altered membrane function. Lovast atin had no effect on brain cholesterol in ApoE-/- mice. Peripheral cholest erol levels were not affected by lovastatin in all three groups of mice. We demonstrate for the first time that lovastatin represents a valid pharmaco logical tool to significantly modulate brain cholesterol levels. NeuroRepor t 12:883-887 (C) 2001 Lippincott Williams & Wilkins.