Long-term effects of forty-hertz auditory stimulation as a treatment of Alzheimer's disease: Insights from an aged monkey model study

• 成果类型: Article
• 署名作者: Wang, Wenchao; Huang, Rongyao; Lv, Longbao; Ma, Xia; Li, Zhenhui; Zhang, Yuhua; Wu, Jing; Wu, Shihao; Xu, Jianglei; Hu, Yingzhou; Turck, Christoph W.; Li, Hao; Hu, Xintian
• 署名单位: Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Yunnan University; Max Planck Society
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2529565123
• 发表日期: 2026-01-13
• 页码: e2529565123
• 关键词: Forty-hertz auditory stimulation; aged monkeys; A beta deposition; A beta levels; Alzheimer's disease; DRUG-DEVELOPMENT PIPELINE; cerebrospinal-fluid; clinical-trials; senile plaques; protein-tau; beta; phosphorylation; limitations; biomarkers; symptoms

摘要

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.