Treatment with controlled-release lovastatin decreases serum concentrations of human β-amyloid (Aβ) peptide

The deposition of β-amyloid (Aβ) in neuronal plaques is believed to be crucial for the initiation and progression of Alzheimer's disease (AD). Studies in vitro have shown that inhibiting cholesterol metabolism with lovastatin, or its active metabolite lovastatin acid, lowers Aβ production. To examine the effects of lovastatin on Aβ in vivo, human subjects who had elevated low-density lipoprotein cholesterol were treated during a double-blind, randomized, placebo-controlled study with 10, 20, 40 or 60 mg once-daily doses of a controlled-release formulation of lovastatin, or matching placebo. Serum Aβ concentrations were measured before and after up to 3 months of treatment. Mean and median changes from baseline in serum Aβ concentrations showed a dose-dependent decrease, and analysis of variance indicated that treatment was statistically significant (p < 0.0348). Differences between the 40- and 60-mg dose groups and placebo were statistically significant (Dunnett's p ≤ 0.05).