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

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

  • McComb M Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
  • Krikheli M Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
  • Uher T Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
  • Browne RW Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, USA.
  • Srpova B Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
  • Oechtering J Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Maceski AM Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Tyblova M Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
  • Jakimovski D Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
  • Ramasamy DP Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
  • Bergsland N Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA; IRCCS, Fondazione Don Carlo Gnocchi, Milan, Italy.
  • Krasensky J Department of Radiology, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Czech Republic.
  • Noskova L Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
  • Fialova L Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
  • Weinstock-Guttman B Department of Neurology, State University of New York, Buffalo, NY, USA.
  • Havrdova EK Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
  • Vaneckova M Department of Radiology, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Czech Republic.
  • Zivadinov R 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.
  • Horakova D Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
  • Kuhle J Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Ramanathan M 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.
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  • 2020-08-08
Published in:
  • Journal of clinical lipidology. - 2020
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/139218
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