Based mainly on rodents studies, forty-hertz (40-Hz) physical stimulation has been regarded as a potential noninvasive treatment for Alzheimer's disease (AD). Considering the brain differences between rodents and humans, the effects of 40-Hz physical stimulation need to be further validated using nonhuman primates before its clinical application. Here, we took advantage of a rare opportunity to expose nine aged rhesus monkeys (26 to 31 y old) to 40-Hz auditory stimulation. Given the strong correlation between cerebrospinal fluid (CSF) A beta and Tau concentrations and corresponding AD pathology in brain parenchyma in clinical practice, we investigated the effects of 40-Hz stimulation on AD pathology by monitoring changes in CSF A beta and Tau concentrations. Our results revealed that 7 consecutive days of 40-Hz auditory stimulation triggered a rapid and significant increase of A beta levels by more than 200%, but no effect on Tau levels in the CSF. Additionally, we observed that the elevation of CSF A beta levels persisted for more than 5 wk after cessation, which had not been reported in any previous studies. After this, a pathological examination of the temporal cortices of 4 of the experimental monkeys was carried out and the data demonstrated that all of them had prevalent extracellular A beta senile plaque pathology, whereas Tau pathology was negative or very weak. These results provide a good explanation for the differences between the CSF A beta and Tau protein levels. Together, these first-time results from monkeys suggest that 40-Hz auditory stimulation has strong potential of a noninvasive AD treatment method.