Transcranial alternating current stimulation (tACS) could improve cognition in patients with Alzheimer's disease (AD). However, the effects of tACS on brain activity remain unclear.The purpose is to investigate the change in regional neuronal activity after tACS in AD patients employing resting-state functional magnetic resonance imaging (rs-fMRI).A total of 46 patients with mild AD were enrolled. Each patient received 30 one-hour sessions of real or sham tACS for three weeks (clinical trial: NCT03920826). The fractional amplitude of low-frequency fluctuations (fALFF) and the regional homogeneity (ReHo) measured by rs-fMRI were calculated to evaluate the regional brain activity.Compared to baseline, AD patients in the real group exhibited increased fALFF in the left middle frontal gyrus-orbital part and right inferior frontal gyrus-orbital part, as well as increased ReHo in the left precentral gyrus and right middle frontal gyrus at the end of intervention. At the 3-month follow-up, fALFF increased in the left superior parietal lobule and right inferior temporal gyrus, as well as ReHo, in the left middle frontal gyrus and right superior medial frontal gyrus. A higher fALFF in the right lingual gyrus and ReHo in the right parahippocampal gyrus were observed in the response group than in the nonresponse group.The findings demonstrated the beneficial effects of tACS on the neuronal activity of the prefrontal cortex and even more extensive regions and provided a neuroimaging biomarker of treatment response in AD patients.