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

J Lipid Res. 2017 Feb;58(2):403-411. doi: 10.1194/jlr.M072751. Epub 2016 Dec 6.

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.

Keywords: brain atrophy; cholesterol; magnetic resonance imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / physiopathology
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Demyelinating Diseases / blood
  • Demyelinating Diseases / diagnostic imaging
  • Demyelinating Diseases / drug therapy
  • Demyelinating Diseases / pathology
  • Female
  • Humans
  • Interferon beta-1a / administration & dosage*
  • Lipids / blood*
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / diagnostic imaging
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Nerve Degeneration / blood
  • Nerve Degeneration / diagnostic imaging
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / pathology

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Lipids
  • Cholesterol
  • Interferon beta-1a