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

J Lipid Res. 2005 Feb;46(2):191-5. doi: 10.1194/jlr.C400005-JLR200. Epub 2004 Dec 1.


In a recent publication [Diestel, A., O. Aktas, D. Hackel, I. Hake, 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 microg/l (median, ranging from 0.4 to 4.6 microg/l), less than 1/1,000 th of the previously reported level. The level of 7-oxocholesterol in CSF from 24 Swedish control patients was 0.9 microg/l (0.3-2.3 microg/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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cholesterol / metabolism
  • Female
  • Humans
  • Ketocholesterols / cerebrospinal fluid*
  • Lipid Metabolism
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Nervous System Diseases / cerebrospinal fluid
  • Oxygen / metabolism
  • Retrospective Studies
  • Sterols / metabolism
  • Time Factors


  • Ketocholesterols
  • Sterols
  • Cholesterol
  • 7-ketocholesterol
  • Oxygen