Numerous findings indicate that ApoEe4 has potential proZelboraf inflammatory functions or reduced anti-inflammatory activity in AD. Our study showed that the AA genotype of rs57095329 could increase the expression level of miR146a and was positively correlated with the expression of inflammatory cytokines, also presenting a stimulatory effect on the inflammatory response. However, no significantly synergistic effect was found between the miR146a polymorphism and the APOE e4 allele in this case-control study. Nevertheless, due to the relatively small number of ApoE subgroups and the less clear relationships between the ApoE allele, miR146a and neuroinflammation in AD, whether there is a correlation between miR146a and ApoE in the pathology of AD will require further study. In another association analysis of the EOAD/LOAD subgroups, our results showed that the AA genotype was associated with an increased risk of AD in the EOAD subgroups. It is well known that mutations in the APP, PS1 and PS2 genes have been mainly discovered in patients with EOAD. APP encodes the amyloid precursor protein found in plaques, and PS1 and PS2 are fundamental components of the csecretase complex involved in the cleavage of APP. All three of these genes contribute to the production of Ab. As mentioned previously, miR146a may play a role in the production of Ab through the miR146a-TSPAN12-ADAM10 pathway. We hypothesized that in addition to the regulating role of miR146a polymorphisms on the neuroinflammation, rs57095329 may also influence the metabolism of APP and eventually increase the generation of Ab42, thus contributing to the risk of EOAD. Numerous reports have associated neuroinflammation with cognitive decline in AD. A clinical study recently reported that AD individuals with a high inflammatory score had a more accelerated decline in their MMSE score over a 3-year period than those with a low inflammatory score. The elevated concentrations of pro-inflammatory cytokines, such as IL1b and IL-6, were also associated with impaired cognitive performance. Notably, as the positive regulator of inflammation in AD, the elevated levels of miR146a may increase the expression of pro-inflammatory cytokines in AD patients. Therefore, it is possible that the functional polymorphism in miR146a may contribute to the cognitive degeneration in AD patients by influencing the inflammatory process in the brain. Our data showed a positive association between the risk-associated AA genotype of rs57095329 and the cognitive deterioration of AD patients, in agreement with the phenomenon that higher levels of IL-1b and IL-6 were produced individuals with the AA genotype as a result of the stimulation. Although the mechanisms underlying this association cannot be directly inferred from this study.