Abstract Background Alzheimer’s disease is a neurodegenerative disorder. Therapeutically, a transplantation of bone marrow mesenchymal stem cells (BMMSCs) can play a beneficial role in animal models of Alzheimer’s disease. However, the relevant mechanism remains to be fully elucidated. Main body Subsequent to the transplantation of BMMSCs, memory loss and cognitive impairment were significantly improved in animal models with Alzheimer’s disease (AD). Potential mechanisms involved neurogenesis, apoptosis, angiogenesis, inflammation, immunomodulation, etc. The above mechanisms might play different roles at certain stages. It was revealed that the transplantation of BMMSCs could alter some gene levels. Moreover, the differential expression of representative genes was responsible for neuropathological phenotypes in Alzheimer’s disease, which could be used to construct gene-specific patterns. Conclusions Multiple signal pathways involve therapeutic mechanisms by which the transplantation of BMMSCs improves cognitive and behavioral deficits in AD models. Gene expression profile can be utilized to establish statistical regression model for the evaluation of therapeutic effect. The transplantation of autologous BMMSCs maybe a prospective therapy for patients with Alzheimer’s disease.