The International Journal of Neuropsychopharmacology

Table of Contents - 2001 - Volume 4, Issue 02  


Rapid Communication

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

Lawrence T.  Friedhoff  a1, Edward I.  Cullen  a1, Neil S. M.  Geoghagen  a2 and Joseph D.  Buxbaum  a2 a3 c1
a1 Aura Laboratories, Inc., Andrx Corporation, 401 Hackensack Avenue, Hackensack, NJ 07601, USA
a2 Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
a3 Neurobiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA

Abstract

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 [less-than-or-eq, slant] 0.05).

(Received December 17 2000)
(Reviewed February 14 2001)
(Revised February 27 2001)
(Accepted February 28 2001)


Key Words: β-Amyloid; Aβ; Alzheimer's disease; controlled-release lovastatin; clinical trial.

Correspondence:
c1 Address for correspondence: Dr J. D. Buxbaum, Mount Sinai School of Medicine, One Gustave L. Levy Place Box 1230, New York, NY 10029, USA. Tel.: (212) 659-8862 Fax: (212) 828-4221 E-mail: buxbaj01@doc.mssm.edu

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