Polymorphisms of the gene encoding the inflammatory cytokine interleukin-6 determine the magnitude of the increase in soluble interleukin-6 receptor levels in Alzheimer's disease. Results of a pilot study

Eur Arch Psychiatry Clin Neurosci. 2003 Feb;253(1):44-8. doi: 10.1007/s00406-003-0405-x.


Interleukin-6 (IL-6) is a multifunctional cytokine involved in the pathogenesis of Alzheimer's disease (AD). The effects of IL-6 are mediated through a specific receptor complex made up of a ligand binding glycoprotein (gp80 or IL-6R) and a signal transducing glycoprotein (gp130). Conflicting results have been reported concerning altered IL-6 or soluble IL-6R (sIL-6R) levels in serum and CSF in AD. This study investigated whether genetic heterogeneity determines the magnitude of the difference in IL-6 and sIL-6R levels in AD. Fifty-eight AD patients and 25 control subjects were included. Plasma and CSF IL-6 and sIL-6R levels were measured and the IL-6 variable number of number repeats ( IL-6vntr) and IL-6 promoter ( IL-6prom) genotypes were determined. sIL-6R levels in plasma and CSF were higher in AD patients than in control subjects. This elevation was striking among non-carriers of the IL-6vntr*C allele and among subjects homozygous for the IL-6prom*C allele whereas no difference in plasma and CSF sIL-6R levels was observed among carriers of the IL-6vntr*C allele and among subjects with the IL-6prom*CG and IL-6prom*GG genotypes. We conclude that plasma and CSF levels of sIL-6R are significantly increased in AD patients and that the magnitude of increase is determined by the IL-6 genotype.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Female
  • Genotype
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / cerebrospinal fluid
  • Interleukin-6 / genetics*
  • Male
  • Pilot Projects
  • Polymorphism, Genetic*
  • Receptors, Interleukin-6 / analysis*
  • Receptors, Interleukin-6 / blood
  • Solubility


  • Biomarkers
  • Interleukin-6
  • Receptors, Interleukin-6