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APOE genotype‐dependent differential influences on MS
Author(s) -
Lahey Matthew,
Langston Zachary,
Affaneh Amira,
Cudaback Eiron
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.659.14
Subject(s) - multiple sclerosis , apolipoprotein e , microglia , immunology , astrocyte , proinflammatory cytokine , myelin , biology , inflammation , immune system , pathogenesis , genotype , central nervous system , disease , neuroscience , medicine , genetics , gene , pathology
Multiple Sclerosis (MS) is an autoimmune disease that demyelinates the central nervous system (CNS) and leads to a loss of neuron conductivity. T helper (Th) cells promote inflammation in the CNS by responding to myelin antigens and activating microglia cells and astrocytes, the resident immune cells of the brain. Proinflammatory cytokines synthesized and secreted by Th cells have profound effects on the brain and represent a possible initiator and key mediator of MS pathogenesis. While the precise molecular and cellular mechanisms underlying CNS sensitivity to Th cells and their secreted products remain poorly understood, genetic risk factors offer important insight to the puzzle. APOE encodes apolipoprotein E and is uniquely polymorphic in humans. Inheritance of the ɛ4 allele is associated with increased disease severity and progression, as well as poorer outcomes in many neurodegenerative diseases, including MS. In addition, APOE genotype determines microglial and astrocyte responses to a wide range of inflammatory stimuli. Here we present data supporting APOE genotype‐dependent differential glial response to MS‐relevant stimuli.