Several anticholesterol drugs, particularly statins, at standard doses can significantly reduce plasma levels of the brain cholesterol degradation product 24S-hydrocholesterol, according to a report in this week's Archives of Neurology.
There is a popular hypothesis already driving clinical trials that statins can help prevent neurodegeneration in Alzheimer's disease. The mechanism by which this might happen is still unfolding, but it may involve either interference with the production of toxic Aβ or interference with directly toxic effects of 24S-hydrocholesterol, or both (see ARF related news story); also, extended comment by Ben Wolozin).
Dieter Lutjohann of the University of Bonn in Germany, a coauthor of the current paper, and colleagues have shown that plasma levels of 24S-OH-Chol are elevated in AD patients (Lutjohann et al., 2000), and that simvastatin could reduce Aβ40 and 24S-OH-Chol levels in the cerebrospinal fluid of AD patients (Simons et al., 2002). However, that study employed very high doses of the statin, and in the current study, lead author Gloria Vega, Myron Weiner, and colleagues at the University of Texas Southwestern Medical Center in Dallas and at the University of Bonn wanted to measure the effect of standard doses used for dyslipidemia.
The researchers measured plasma levels of 24S-hydrocholesterol, ApoE, and other cholesterols in AD patients taking three different statins (40 mg/day) along with extended-release niacin (1 g/day). After six weeks of treatment, each of the statins had reduced levels of 24S-hydrocholesterol by approximately 20 percent and LDL cholesterol by 34.9 percent. Niacin reduced 24S-hydrocholesterol by 10 percent and LDL cholesterol by 18.1 percent. There were no reductions in ApoE plasma concentration from any treatment.
"It would be of interest to determine whether a combination of a statin and extended-release niacin has an additive effect on levels of 24S-hydroxycholesterol," write the authors.—Hakon Heimer
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- Lütjohann D, Papassotiropoulos A, Björkhem I, Locatelli S, Bagli M, Oehring RD, Schlegel U, Jessen F, Rao ML, von Bergmann K, Heun R. Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J Lipid Res. 2000 Feb;41(2):195-8. PubMed.
- Simons M, Schwärzler F, Lütjohann D, von Bergmann K, Beyreuther K, Dichgans J, Wormstall H, Hartmann T, Schulz JB. Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol. 2002 Sep;52(3):346-50. PubMed.
- Vega GL, Weiner MF, Lipton AM, von Bergmann K, Lutjohann D, Moore C, Svetlik D. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol. 2003 Apr;60(4):510-5. PubMed.