A body of evidence indicates that inflammation plays a pivotal role in AD pathogenesis. IL-18 is a pro-inflammatory cytokine produced in the brain, emerging to be implicated in AD. Although no differences in circulating IL-18 levels were measured between AD patients and controls, a significant increased production of IL-18 was obtained from stimulated blood mononuclear cells of AD patients. This was true particularly in AD subjects carrying the C/C genotype at the -607 position of IL-18 gene promoter. Furthermore, a significant correlation between IL-18 production and cognitive decline was observed in AD patients. Overall, these data indicate that IL-18-related inflammatory pathways, probably also in virtue of polymorphic IL-18 gene influence, are exacerbated in AD patients, and that this cytokine may indeed participate in pathogenic processes leading to dementia.