Treatment with controlled-release lovastatin decreases serum concentrations of human beta-amyloid (A beta) peptide.
The deposition of beta-amyloid (A beta) 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 A beta production. To examine the effects of lovastatin on A beta 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 A beta concentrations were measured before and after up to 3 months of treatment. Mean and median changes from baseline in serum A beta 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 < or = 0.05).
Friedhoff
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Aura Laboratories, Inc., Andrx Corporation, Hackensack, NJ 07601, USA.
Cullen
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Geoghagen
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Buxbaum
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D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000097:blood*; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008148:Lovastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D003692:Delayed-Action Preparations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin