Journal
JOURNAL OF CLINICAL LIPIDOLOGY
Volume 14, Issue 5, Pages 675-+Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2020.07.001
Keywords
Neurofilament light chain; Lipid; Cholesterol; Apolipoproteins; Blood-brain barrier; Cerebrospinal fluid; Brain lesions; MRI; Disease onset; Multiple sclerosis
Categories
Funding
- Charles University Grant Agency (GAUK) [230217]
- Czech Ministry of Education [Progress Q27/LF1]
- Czech Ministry of Health [RVOVFN64165]
- AZV [NV18-08-00062, NV18-04-00168]
- Department of Defense Multiple Sclerosis Research Program for the Office of the Congressionally Directed Medical Research Programs (CDMRP) [MS190096]
- Biogen
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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. (C) 2020 National Lipid Association. All rights reserved.
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