Neuroprotective associations of apolipoproteins A-I and A-II with neurofilament levels in early multiple sclerosis

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.