BACKGROUND: The role of cholesterol homeostasis in neuroaxonal injury in multiple sclerosis is not known. OBJECTIVE: The objective of the study is to investigate the associations of cerebrospinal fluid (CSF) and serum neurofilament light chain levels (CSF-NfL and sNfL, respectively), which are biomarkers of neuroaxonal injury, with cholesterol biomarkers at the clinical onset of multiple sclerosis. METHODS: sNfL, serum cholesterol profile (total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), serum apolipoprotein (Apo) levels (ApoA-I, ApoA-II, ApoB, and ApoE), and albumin quotient were obtained for 133 patients (63% female, age: 29.9 ± 8.0 years) during the first demyelinating event. CSF-NfL was available for 103 (77%) patients. RESULTS: CSF-NfL and sNfL were negatively associated with serum ApoA-II (P = .005, P < .001) and positively associated with albumin quotient (P < .001, P < .0001). In addition, higher CSF-NfL was associated with lower serum ApoA-I (P = .009) levels and higher sNfL was associated with lower high-density lipoprotein cholesterol (P = .010). In stepwise regression, age (P = .045), serum ApoA-II (P = .022), and albumin quotient (P < .001) were associated with CSF-NfL; albumin quotient (P = .002) and ApoA-II (P = .001) were associated with sNfL. Path analysis identified parallel pathways from ApoA-II (P = .009) and albumin quotient (P < .001) to the sNfL outcome that were mediated by CSF-NfL (P < .001). The associations of CSF-NfL with ApoA-I (P = .014) and ApoA-II (P = .015) and sNfL with ApoA-II (P < .001) remained significant after adjusting for number of contrast-enhancing lesions and T2 lesion volume. CONCLUSION: Lower serum ApoA-II and ApoA-I levels are associated with greater neuroaxonal injury as measured by CSF-NfL.

Buffalo Neuroimaging Analysis Center Department of Neurology State University of New York Buffalo NY USA

Buffalo Neuroimaging Analysis Center Department of Neurology State University of New York Buffalo NY USA; Center for Biomedical Imaging at Clinical Translational Science Institute University at Buffalo State University of New York Buffalo NY USA

Buffalo Neuroimaging Analysis Center Department of Neurology State University of New York Buffalo NY USA; IRCCS Fondazione Don Carlo Gnocchi Milan Italy

Department of Biotechnical and Clinical Laboratory Sciences State University of New York Buffalo NY USA

Department of Neurology and Center of Clinical Neuroscience Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Department of Neurology State University of New York Buffalo NY USA

Department of Pharmaceutical Sciences State University of New York Buffalo NY USA

Department of Pharmaceutical Sciences State University of New York Buffalo NY USA; Department of Neurology State University of New York Buffalo NY USA

Department of Radiology Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Neurologic Clinic and Policlinic Departments of Medicine Biomedicine and Clinical Research University Hospital Basel University of Basel Basel Switzerland

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