Interleukin-6 promoter polymorphism: risk and pathology of Alzheimer's disease

Inflammatory and immune responses are involved in the pathogenesis of Alzheimer's disease (AD). Interleukin-6 (IL-6), an inflammatory cytokine, is thought to play a role in neurodegeneration of the central nervous system and has been associated with increased amyloid precursor protein expression in vitro and greater cognitive decline. Previously a C-174G polymorphism in the promoter of IL-6, which influences expression in vitro, has been found associated in some studies but not all. We investigated this polymorphism in a large independent UK sample of AD cases (n = 356) and controls (n 434) but found no association. We extended the study to genotype/phenotype correlations but found no correlation with age of onset (n = 338), brain amyloid load (n = 126) or Tau load (n = 101), brain microglial cell load (n = 65) or brain reactive astrocytes (n = 127). Our data do not support a pathogenic role in AD for the C-174G polymorphism in isolation.