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

J Clin Lipidol. 2020 Sep-Oct;14(5):675-684.e2. doi: 10.1016/j.jacl.2020.07.001. Epub 2020 Jul 9.


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.

Keywords: Apolipoproteins; Blood-brain barrier; Brain lesions; Cerebrospinal fluid; Cholesterol; Disease onset; Lipid; MRI; Multiple sclerosis; Neurofilament light chain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoprotein A-I / blood*
  • Apolipoprotein A-II / blood*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / pathology
  • Neurofilament Proteins / cerebrospinal fluid*
  • Neuroprotective Agents / blood
  • Neuroprotective Agents / cerebrospinal fluid
  • Prognosis
  • Prospective Studies


  • APOA1 protein, human
  • APOA2 protein, human
  • Apolipoprotein A-I
  • Apolipoprotein A-II
  • Neurofilament Proteins
  • Neuroprotective Agents
  • neurofilament protein L