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

Mason McComb; Maggie Krikheli; Tomas Uher; Richard W Browne; Barbora Srpova; Johanna Oechtering; Aleksandra Maleska Maceski; Michaela Tyblova; Dejan Jakimovski; Deepa P Ramasamy; Niels Bergsland; Jan Krasensky; Libuse Noskova; Lenka Fialova; Bianca Weinstock-Guttman; Eva Kubala Havrdova; Manuela Vaneckova; Robert Zivadinov; Dana Horakova; Jens Kuhle; Murali Ramanathan

doi:10.1016/j.jacl.2020.07.001

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.

Authors

Mason McComb¹, Maggie Krikheli¹, Tomas Uher², Richard W Browne³, Barbora Srpova², Johanna Oechtering⁴, Aleksandra Maleska Maceski⁴, Michaela Tyblova², Dejan Jakimovski⁵, Deepa P Ramasamy⁵, Niels Bergsland⁶, Jan Krasensky⁷, Libuse Noskova⁸, Lenka Fialova⁸, Bianca Weinstock-Guttman⁹, Eva Kubala Havrdova², Manuela Vaneckova⁷, Robert Zivadinov¹⁰, Dana Horakova², Jens Kuhle⁴, Murali Ramanathan¹¹

Affiliations

¹ Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
² Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
³ Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, USA.
⁴ Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
⁵ Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
⁶ Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA; IRCCS, Fondazione Don Carlo Gnocchi, Milan, Italy.
⁷ Department of Radiology, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Czech Republic.
⁸ Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
⁹ Department of Neurology, State University of New York, Buffalo, NY, USA.
¹⁰ 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.
¹¹ Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA; Department of Neurology, State University of New York, Buffalo, NY, USA. Electronic address: Murali@Buffalo.Edu.

PMID: 32758395
DOI: 10.1016/j.jacl.2020.07.001

Abstract

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

Substances

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