title: Human cytokine response to ex vivo amyloid-beta stimulation is mediated by genetic factors.
abstract: Through its ability to induce the enhanced release and production of cytokines, amyloid-beta is responsible for the chronic inflammatory response that contributes to Alzheimer's disease (AD). Determining whether the response of monocytes to amyloid-beta stimulation is under genetic control may help understand the basis of why some people are more prone to develop neuronal degeneration than others. In the current study we investigated the heritability of the cytokine (IL-10, IL-6, IL-1beta, IL-1ra, TNF-alpha) production capacity upon ex vivo stimulation with amyloid-beta in whole blood samples of 222 twins and 85 singleton siblings from 139 extended twin families. It was found that individual differences in amyloid-beta induced cytokine production capacity are to a large extent of genetic origin, with heritability estimates ranging from 55% (IL-1beta) to 68% (IL-6). We conclude that genes influencing amyloid-beta-induced cytokine response may provide clues to the progression of AD pathology.
authors.affiliation: Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands. danielle@psy.vu.nl
authors.forename: Danielle
authors.initials: D
authors.lastname: Posthuma
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics; D004777:Environment; D004926:Escherichia coli; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10