Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients

Tomas Uher, Kelly Fellows, Dana Horakova, Robert Zivadinov, Manuela Vaneckova, Lukas Sobisek, Michaela Tyblova, Zdenek Seidl, Jan Krasensky, Niels Bergsland, Bianca Weinstock-Guttman, Eva Havrdova, Murali Ramanathan

Research output: Contribution to journalArticlepeer-review

Abstract

The purpose of this work was to determine whether changes in cholesterol profiles after interferon-β (IFN-β) 1a treatment initiation following the first demyelinating event suggestive of multiple sclerosis are associated with clinical and MRI outcomes over 4 years. A group of 131 patients (age: 27.9 ± 7.8 years, 63% female) with serial 3-monthly clinical and 12-monthly MRI follow-ups over 4 years were investigated. Serum cholesterol profiles, including total cholesterol (TC), HDL cholesterol (HDL-C), and LDL cholesterol (LDL-C) were obtained at baseline, 1 month, 3 months, and every 6 months thereafter. IFN-β1a initiation caused rapid decreases in serum HDL-C, LDL-C, and TC within 1 month of IFN-β1a initiation (all P < 0.001) that returned slowly toward baseline. In predictive mixed model analyses, greater percent decreases in HDL-C after 3 months of IFN-β1a treatment initiation were associated with less brain atrophy over the 4 year time course, as assessed by percent brain volume change (P < 0.001), percent gray matter volume change (P < 0.001), and percent lateral ventricle volume change (P = 0.005). Decreases in cholesterol biomarkers following IFN-β1a treatment are associated with brain atrophy outcomes over 4 years. Pharmacological interventions targeting lipid homeostasis may be clinically beneficial for disrupting neurodegenerative processes.

Original languageEnglish
Pages (from-to)403-411
Number of pages9
JournalJournal of Lipid Research
Volume58
Issue number2
DOIs
Publication statusPublished - 2017

Keywords

  • Brain atrophy
  • Cholesterol
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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