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Interleukin-6 (IL-6) is a multifunctional cytokine playing a crucial role in inflammation and tissue injury. A role for this molecule in neurodegeneration and Alzheimer's disease (AD) has been proposed. The aim of this study was to evaluate the association between a common polymorphism of the IL-6 gene promoter and AD in the Italian population. We found that the frequency of the GG genotype was significantly higher in AD patients than controls on both univariate (p< 0.0001) and multivariate analysis (p< 0.0001). In contrast, the CC genotype seems to be associated with a reduced risk of disease (p< 0.0001). Our data indicate that the IL-6 gene polymorphism is associated with AD in Italians and confirm that IL-6 is crucial in the pathophysiology of neurodegenerative disorders.