Objective To explore the role of miR-29c involved in Alzheimers disease． Methods Using highly sensitive microarray-based procedures，we identified microRNA increased in the 3，6，9 month-old APPswe /PSΔE9 doubletransgenic mouse brain，and then validated by real time PCR． Predicted target gene of miRNA were to be chosen though miRNA target databases． We constructed the miR-29c expression vector and transfected it into SH-SY5Y and HEK-293T cell line to validate our hypothesis． We generated the dual-luciferase reporter vectors of APP mRNA 3’UTR and mutant 3’ UTR to identify the binding site of miR-29c by luciferase assay． Results Higherly-expressed miR-29c was measured by microarray and then confirmed by real time PCR in the 3，6，9-month-old APPswe /PSΔE9 double-transgenic mouse brain ．APP is predicted to be downregulated by miR-29c by miRBase databases． We demonstrated APP protein decreased in overexpressed miR-29c SH-SY5Y cell line by Western blot． Then we confirmed miR-29c can decreased APP protein expression by cotransfecting miR-29c expression vector with APP cDNA vector( involved 3’UTR in full length) to HEK- 293T cell lines． In particular，we had not detected the target site of miR-29c in the APP mRNA 3’UTR by luciferase assay in HEK-293T cell line． Conclusions miR-29c can downregulate APP expression in vitro，but the target site may be not in the APP mRNA 3’UTR．