Leading to a decrease in the total amount of mature miR146a, which in turn influences the transcription of target genes and the pathogenesis of the disease. Several immune and inflammatory-related diseases are associated with rs2910164 polymorphisms, such as papillary thyroid carcinoma. Behc¸et’s disease, ulcerative colitis, adult glioma and prostate cancer Recently, another genetic variant, rs57095329, in the miR146a promoter was reported to affect the level of mature miR146a by reducing the protein-binding affinity of the miR146a promoter, and this polymorphism has been associated with systemic lupus erythematosus susceptibility. However, to the best of our knowledge, no studies have examined the association of miR146a polymorphisms with the risk of AD. In the present study, we conducted an association analysis to ascertain whether the two functional polymorphisms of miR146a could contribute to the risk of AD in the Chinese population. SNPs present on precursor and mature miRNAs have been shown to influence the level of the mature miRNA and have been shown to be associated with various diseases. In the present study, two SNPs of functional significance in miR146a, rs2910164 and rs57095329, were chosen to evaluate their association with AD. As expected, our results confirmed that the two SNPs could both affect the levels of mature miR146a, which is consistent with previous reports. Moreover, our study identified that the AA genotype of the rs57095329 polymorphism, but not rs2910164, was associated with an increased risk for cognitive decline in AD patients. To our knowledge, this is the first study to report the potential role of genetic variants of miR146a in AD susceptibility. The G/A polymorphism of rs57095329 is located in the promoter region of miR146a with a binding site for the V-Ets oncogene homologue 1. The A allele of rs57095329 interferes with Ets-1 binding and leading to a higher expression level of mature miR146a. Meanwhile, increasing evidence indicates that miR146a plays a role in stimulating the inflammation response in the brains of AD patients, and our results also confirm that the AA genotype could increased the mature level of miR146a and elevated the level of proinflammatory cytokines IL-1b and IL-6, so we speculate that the change in the expression level of miR146a by the rs57095329 polymorphism may in turn regulated the inflammation response in the brains of AD patients, which could further contribute to the AD susceptibility. Notably, Ets-1 was reported to be widely expressed in the cortex and hippocampus, and particularly high in the brains of AD patients, suggesting that rs57095329 may have a stronger effect on the expression of miR146a on account of the high level of ETS-1 in AD brain, also Rapamycin mTOR inhibitor supported this view. ApoE polymorphic alleles are the main genetic determinants of LOAD risk.