A role for Apolipoprotein A-I in the pathogenesis of multiple sclerosis

J Neuroimmunol. 2014 Dec 15;277(1-2):176-85. doi: 10.1016/j.jneuroim.2014.10.010. Epub 2014 Oct 30.

Abstract

Apolipoprotein A1 (Apo A-I), the most abundant component of high-density lipoprotein (HDL), is an anti-inflammatory molecule, yet its potential role in the pathogenesis of multiple sclerosis (MS) has not been fully investigated. In this study, Western blot analyses of human plasma showed differential Apo A-I expression in healthy controls compared to MS patients. Further, primary progressive MS patients had less plasma Apo A-I than other forms of MS. Using experimental allergic encephalomyelitis (EAE) as a model for MS, Apo A-I deficient mice exhibited worse clinical disease and more neurodegeneration concurrent with increased levels of pro-inflammatory cytokines compared to wild-type animals. These data suggest that Apo A-I plays a role in the pathogenesis of EAE, a model for MS, creating the possibility for agents that increase Apo A-I levels as potential therapies for MS.

Keywords: Apolipoprotein A-I; EAE; Multiple sclerosis; Neurological disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Animals
  • Apolipoprotein A-I / blood
  • Apolipoprotein A-I / deficiency
  • Apolipoprotein A-I / genetics*
  • Case-Control Studies
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Electrophoresis, Gel, Two-Dimensional
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Evoked Potentials, Visual / genetics
  • Evoked Potentials, Visual / physiology
  • Female
  • Fluoresceins
  • Freund's Adjuvant / toxicity
  • Gene Expression Regulation / genetics
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / pathology*
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Peptide Fragments / toxicity

Substances

  • Apolipoprotein A-I
  • Cytokines
  • Fluoresceins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • fluoro jade
  • myelin oligodendrocyte glycoprotein (35-55)
  • Freund's Adjuvant