Objective To explore the role of mir-153 in Alzheimer’s disease． Methods Detected the expression of mir-153 in the brain tissue of 3 months old APPswe /PSΔE9 mouse by means of microRNA array and Real-time PCR．Developed the stable transfection cell line that expressed mir-153 on a high level． Explored the expression of RTN4 protein by western-blot． Constructed the wild type and mutation type RTN4 3’UTR luciferase reporter vecter，cotransfected them with mir-153 expression vecter or negative control into 293T cell，detected the relative activity of Renilla Luciferase to check the binding site of mir-153 on RTN4’s mRNA． Results The result of microRNA arry and Real-time PCR all indicated in 3 months old APP swe /PSΔE9 mouse，the expression of mir-153 significantly decreased when compared to the wild contro on the same age． In stable transfection cell line expressing high level mir-153，the expression of RTN4 protein was downregulated． When compared to negative control / wild type RTN4 3’UTR contransfection group，Cotransfection mir-153 together with wild type RTN4 3’UTR． can strikingly shutdown the relative activity of Renilla Luciferase ( P ＜0. 05) ，however mir-153 / mutation type RTN4 3’UTR cotransfection group couldn’t reach any significant difference．Conclusions In 3 months old APPswe /PSΔE9 mouse’s brain，the expression of mir-153 is abnormal． Mir-153 can regulate the expression of RTN4 on protein level． The regulation effect of mir-153 on RTN4 is achieved by binding the specific site lie in 839-845 bp of RTN4 3’UTR．