Increasing evidence indicates that the beta2-adrenergic receptor (beta2-AR) may play an important role in Alzheimer's disease (AD). We investigated the effect of two polymorphisms in the beta2-AR gene: Gly16Arg and Gln27Glu for the risk of sporadic Late Onset Alzheimer's Disease (LOAD) in 109 patients and 109 healthy controls matched for sex and age in a Han Chinese population. Results revealed that both the 16Gly allele and the 27Glu allele of the beta2-AR gene were associated with an increased risk of LOAD (P=0.009, OR=1.652 and P=0.002, OR=2.846, respectively), and they also showed a highly significant interaction with the Apolipoprotein E gene (APOE) epsilon4 allele (OR=4.200 and 9.441, respectively). Examination of the haplotypes identified the Gly16Glu27 haplotype to increase the risk of LOAD (P=0.004). Our results suggest that variations in the beta2-AR gene play an important role in the pathogenesis of sporadic LOAD, and interact with the epsilon4 allele to markedly increase the LOAD risk.