Multiple Sclerosis and Related Disorders | February 25, 2021

McComb M, Browne RW, Bhattacharya S, Bodziak ML, Jakimovski D, Weinstock-Guttman B, Kuhle J, Zivadinov R and Ramanathan M

Multiple sclerosis and related disorders. 2021;50:102864

DOI: https://doi.org/10.1016/j.msard.2021.102864

This study was performed using a Simoa Homebrew assay.

Abstract

Background

Serum neurofilament light chain (sNfL) is an established marker of neuroaxonal injury in multiple sclerosis (MS).

Objectives

To investigate if oxysterols produced from non-enzymatic and enzymatic cholesterol oxidation are differentially associated with sNfL measurements in MS.

Methods

This 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.

Results

The 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.

Conclusions

7KC and 7βHC, produced by ROS-mediated cholesterol oxidation are associated with neuroaxonal injury as assessed by sNfL in MS.