Alzheimer’s disease (AD) is one of the major causes of death that currently cannot be reversed or slowed. Fornix, a major output tract of the hippocampus, has been shown to be a promising target for DBS therapy in AD patients. In this study, triple-transgenic Alzheimer’s mice were used to investigate the changes of white matter integrity and the cognitive functions after the DBS-fornix therapy. We found improvement of the cognition and increased white matter integrity after that DBS-fornix therapy in AD mice. It suggested that the DBS-fornix therapy may be a potential therapeutic intervention of AD.