Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease

Gloria Lena Vega, Myron F. Weiner, Anne M. Lipton, Klaus Von Bergmann, Dieter Lütjohann, Carol Moore, Doris Svetlik

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Abstract

Background: The statin treatment of dyslipidemia is associated with a reduced risk of development of Alzheimer disease (AD). The effect may be mediated by a reduction in cholesterol biosynthesis in the brain, by lowering levels of apolipoprotein E (apo E)-containing lipoproteins, or by pleitropic effects such as reduction in β-amyloid production. In the brain, cholesterol from damaged or dying neurons is converted to 24S-hydroxycholesterol by cholesterol 24-hydroxylase (CYP46). The oxysterol is subsequently transferred across the blood-brain barrier, transported to the liver by low-density lipoproteins (LDLs), and excreted as bile acids. Most of plasma 24S-hydroxycholesterol is derived from brain cholesterol; consequently, plasma levels of the oxysterol reflect brain cholesterol catabolism. Objective: To examine the effect of 3 statins and a non-statin hypolipidemic agent on plasma levels of 24S-hydroxycholesterol and apo E in patients with AD. Study Design: The study had a sequential parallel design. It was open-labeled and involved lipoprotein and 24S-hydroxycholesterol evaluations at baseline and at 6 weeks of treatment with 40 mg of lovastatin, simvastatin, or pravastatin sodium per day, or 1 g of extended-release niacin per day. Blood samples were drawn after a 12-hour fast for measurement of plasma sterols, oxysterols, lipoprotein cholesterol, and levels of apo E, plasma transaminases, and glucose. Measurements were made at baseline and during treatment. Results: Statin treatment reduced levels of plasma lathosterol by 49.5%, 24S-hydroxycholesterol by 21.4%, LDL cholesterol by 34.9%, and total cholesterol by 25%. The ratios of lathosterol-campesterol and 24S-hydroxycholesterol-LDL cholesterol were reduced significantly, but the ratio of 24S-hydroxycholesterol-total cholesterol was unchanged. Extended-release niacin also significantly reduced levels of 24S-hydroxycholesterol by 10% and LDL cholesterol by 18.1%. None of the agents lowered plasma concentration of apo E. Conclusions: Statins lowered levels of plasma 24S-hydroxycholesterol without affecting levels of apo E. The LDL lowering was more pronounced than 24S-hydroxycholesterol reductions. The effect of statins on LDL partially explains the reduction of plasma oxysterol level.

Original languageEnglish (US)
Pages (from-to)510-515
Number of pages6
JournalArchives of Neurology
Volume60
Issue number4
DOIs
Publication statusPublished - Apr 1 2003

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Vega, G. L., Weiner, M. F., Lipton, A. M., Von Bergmann, K., Lütjohann, D., Moore, C., & Svetlik, D. (2003). Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Archives of Neurology, 60(4), 510-515. https://doi.org/10.1001/archneur.60.4.510