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

Valerio Leoni, Dieter Lütjohann, Thomas Masterman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)191-195
Number of pages5
JournalJournal of Lipid Research
Volume46
Issue number2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • 24S-hydroxycholesterol
  • 27-hydroxycholesterol
  • Lipid peroxidation
  • Neurological disease
  • Oxysterols

ASJC Scopus subject areas

  • Endocrinology

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