In the brains of Alzheimer's disease (AD) patients, microglia cells are activated and produce inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha). A recent study conducted in Northern Ireland showed that a polymorphism in the promotor region (-850) of the TNF-alpha gene increased the risk of AD associated with carriage of the apolipoprotein E (APOE) epsilon 4 allele. In a case-control study restricted to a population from Northern Spain and utilizing 321 sporadic AD patients and 312 control subjects, we have found that the -850 TNF-alpha polymorphism does not interact with the APOE gene to increase the risk associated with the epsilon 4 allele.