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Journal of Lipid Research, Vol. 46, 191-195, February 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Rapid Communication

Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis

Valerio Leoni^*, Dieter Lütjohann^1, and Thomas Masterman

^* Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital in Huddinge, Stockholm, Sweden
Department of Clinical Pharmacology, University of Bonn, Bonn, Germany
Division of Neurology, NEUROTEC, Karolinska Institutet, Stockholm, Sweden

¹ To whom correspondence should be addressed. e-mail: dieter.luetjohann{at}ukb.uni-bonn.de

ABSTRACT

In a recent publication [Diestel, A., O. Aktas, D. Hackel, I. Häke, S. Meier, C. S. Raine, R. Nitsch, F. Zipp, and O. Ullrich. 2003. Activation of microglial poly (ADP-ribose)-polymerase-1 by cholesterol breakdown products during neuroinflammation: a link between demyelination and neuronal damage. J. Exp. Med. 198: 1729–1740], extremely high levels of 7-oxocholesterol were reported in cerebrospinal fluid (CSF) of 11 patients with multiple sclerosis (MS) [7.4 ± 0.3 mg/l (mean ± SEM)]. The corresponding level of 12 subjects with other kinds of neurological diseases was reported to be 0.5 ± 0.1 mg/l. Such high levels of 7-oxocholesterol were found to cause neuronal damage of living brain tissues. Using a highly accurate method for an assay of 7-oxocholesterol based on isotope dilution-mass spectrometry and anaerobic conditions during workup, we found that the level of 7-oxocholesterol in CSF from 29 Swedish patients with MS was only 1.2 µg/l (median, ranging from 0.4 to 4.6 µg/l), less than 1/1,000th of the previously reported level. The level of 7-oxocholesterol in CSF from 24 Swedish control patients was 0.9 µg/l (0.3–2.3 µg/l), slightly but significantly lower than the CSF level in MS patients (P = 0.002). In vitro-induced lipid peroxidation of the endogenous cholesterol in CSF increased the level of 7-oxygenated cholesterol metabolites, particularly 7-oxocholesterol, up to 0.3 mg/l.

These results are discussed in relation to the fact that 7-oxygenated steroids are easily artificially formed by autoxidation of cholesterol during workup procedures and analysis of sterols and oxysterols from biological samples.

Abbreviations: ABAP, 2,2'-azobis-2-amidinopropane hydrochloride; BHT, 3,5-di-tert-butyl-4-hydroxytoluene; CSF, cerebrospinal fluid; ID-MS, isotope dilution-mass spectrometry; MS, multiple sclerosis; 24OHC, 24S-hydroxycholesterol; 27OHC, 27-hydroxycholesterol; SIM, selected ion monitoring; TMSi, trimethylsilyl

Supplementary key words 27-hydroxycholesterol • 24S-hydroxycholesterol • neurological disease • lipid peroxidation • oxysterols

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