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.
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.
Bagli
Metin
M
Department of Psychiatry, University of Bonn, Venusberg, 53105 Bonn, Germany.
Papassotiropoulos
Andreas
A
Hampel
Harald
H
Becker
Karin
K
Jessen
Frank
F
Bürger
Katharina
K
Ptok
U
U
Rao
Marie Luise
ML
Möller
Hans-Jürgen
HJ
Maier
Wolfgang
W
Heun
Reinhard
R
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D008297:Male; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D019947:Receptors, Interleukin-6 / Q000032:analysis* / Q000097:blood; D012995:Solubility
D015415:Biomarkers; D015850:Interleukin-6; D019947:Receptors, Interleukin-6