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

Mason McComb; Richard W Browne; Sonia Bhattacharya; Mary Lou Bodziak; Dejan Jakimovski; Bianca Weinstock-Guttman; Jens Kuhle; Robert Zivadinov; Murali Ramanathan

doi:10.1016/j.msard.2021.102864

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

Mult Scler Relat Disord. 2021 May:50:102864. doi: 10.1016/j.msard.2021.102864. Epub 2021 Feb 26.

Authors

Mason McComb¹, Richard W Browne², Sonia Bhattacharya², Mary Lou Bodziak², Dejan Jakimovski³, Bianca Weinstock-Guttman⁴, Jens Kuhle⁵, Robert Zivadinov⁶, Murali Ramanathan⁷

Affiliations

¹ Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, United States.
² Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, United States.
³ Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, United States.
⁴ Jacobs Comprehensive MS Treatment and Research Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, United States.
⁵ Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
⁶ Jacobs Comprehensive MS Treatment and Research Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, United States; Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, United States.
⁷ Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, United States; Jacobs Comprehensive MS Treatment and Research Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, United States. Electronic address: Murali@Buffalo.Edu.

PMID: 33677412
DOI: 10.1016/j.msard.2021.102864

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.

Keywords: 7-ketocholesterol; 7β-hydroxycholesterol; Apolipoprotein E; Cholesterol oxidation; Multiple sclerosis; Oxidative stress; Reactive oxygen species.

MeSH terms

Humans
Hydroxycholesterols
Intermediate Filaments
Ketocholesterols
Longitudinal Studies
Multiple Sclerosis*

Substances

Hydroxycholesterols
Ketocholesterols
cholest-5-en-3 beta,7 alpha-diol
7-ketocholesterol