{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:57:27Z","timestamp":1792717047978,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"2","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,1,13]]},"abstract":"<jats:p>Based mainly on rodents studies, forty-hertz (40-Hz) physical stimulation has been regarded as a potential noninvasive treatment for Alzheimer\u2019s 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\u03b2 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\u03b2 and Tau concentrations. Our results revealed that 7 consecutive days of 40-Hz auditory stimulation triggered a rapid and significant increase of A\u03b2 levels by more than 200%, but no effect on Tau levels in the CSF. Additionally, we observed that the elevation of CSF A\u03b2 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\u03b2 senile plaque pathology, whereas Tau pathology was negative or very weak. These results provide a good explanation for the differences between the CSF A\u03b2 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.<\/jats:p>","DOI":"10.1073\/pnas.2529565123","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T20:02:28Z","timestamp":1767643348000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Long-term effects of forty-hertz auditory stimulation as a treatment of Alzheimer\u2019s disease: Insights from an aged monkey model study"],"prefix":"10.1073","volume":"123","author":[{"given":"Wenchao","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences","place":["Kunmin, China"]},{"name":"National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic and Genetic Analysis 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