The cholesterol autoxidation products, 7-ketocholesterol and 7β-hydroxycholesterol are associated with serum neurofilaments in multiple sclerosis

Abstract

BackgroundSerum neurofilament light chain (sNfL) is an established marker of neuroaxonal injury in multiple sclerosis (MS). ObjectivesTo investigate if oxysterols produced from non-enzymatic and enzymatic cholesterol oxidation are differentially associated with sNfL measurements in MS. MethodsThis longitudinal study included 62 relapsing-remitting (RR-MS) and 36 progressive MS (PMS) patients with baseline and 5-year follow-up measures of serum levels of 6 oxysterols, sNfL and lipids. The oxysterols, 24-hydroxycholesterol (24HC), 25HC, 27HC, 7αHC, 7βHC and 7-ketocholesterol (7KC), were measured using liquid chromatography-mass spectrometry. sNfL was measured using single molecular array assay. Serum high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were obtained from a lipid profile. ResultsThe enzymatically produced oxysterols 24HC, 25HC, 27HC and 7αHC were not associated with sNfL. However, baseline levels of reactive oxygen species (ROS) produced oxysterols, 7KC (p = 0.032) and 7βHC (p = 0.0025), were positively associated with sNfL levels at follow-up. Follow-up 7KC (p = 0.038) levels were also associated with follow-up sNfL levels. The associations of 7KC or 7βHC with sNfL remained significant after adjusting for LDL-C or HDL-C. Conclusions7KC and 7βHC, produced by ROS-mediated cholesterol oxidation are associated with neuroaxonal injury as assessed by sNfL in MS.