There are several major pathological changes in Alzheimer’s disease, including apoptosis of cho-linergic neurons, overactivity or overexpression ofβ-site amyloid precursor protein cleaving enzyme 1 (BACE1) and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein (Aβ) production, and introduced it into the pSilenCircle vector to construct a short hairpin (shRNA) expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing Aβprotein production. We anticipate that this technique combining celltransplantation and gene ther-apy wil open up novel therapeutic avenues for Alzheimer’s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.