A chronic inflammatory process with activation of microglial cells contribute to the neurodegeneration associated with Alzheimer's disease (AD). Estrogen could protect the brain from neurodegeneration by augmenting the secretion of the anti-inflammatory interleukin (IL)-10 from microglial cells. In a case-control study in 231 AD patients and 194 healthy controls, we examined whether the combined effects between the genes coding for aromatase (a critical enzyme in the peripheral synthesis of estrogens) and IL-10 might be responsible for susceptibility to AD. Subjects carrying both the aromatase (5 -UTR) GG and the IL-10 (-1082) GG genotypes had a six times lower risk of developing AD than subjects without these risk genotypes (OR = 0.17, 95% CI = 0.04-0.77, P = 0.02).