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

Valerio Leoni, Dieter Lütjohann, and Thomas Masterman

Department of Clinical Pharmacology, University of Bonn, Bonn 53105

Corresponding Author: dieter.luetjohann{at}ukb.uni-bonn.de

In a recent publication by Diestel et al. extremely high levels of 7-oxocholesterol were reported in cerebrospinal fluid of eleven patients with multiple sclerosis to be 7.4 +/- 0.3 mg/L (mean +/- SEM). The corresponding levels of 12 subjects with other kinds of neurological diseases were 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 work up, we found that the levels of 7-oxocholesterol in cerebrospinal fluid from 29 Swedish patients with multiple sclerosis were only 1.2 µg/L (median, ranging from 0.4 to 4.6 µg/L), less than 1/1000 of the previously reported levels. The levels of 7-oxocholesterol in cerebrospinal fluid from 24 Swedish control patients were 0.9 µg/L (0.3 – 2.3 µg/L), slightly, but significantly lower than the cerebrospinal fluid levels in multiple sclerosis patients (p = 0.002). In vitro induced lipid peroxidation of the endogenous cholesterol in cerebrospinal fluid increased the levels of 7-oxygenated cholesterol metabolites, particularly 7-oxocholesterol, up to about 0.3 mg/L. The results are discussed in relation to the fact that 7-oxygenated steroids are easily artificially formed by autoxidation of cholesterol during work up procedure and analysis of sterols and oxysterols from biological samples.

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