Long-term effects of forty-hertz auditory stimulation as a treatment of Alzheimer’s disease: Insights from an aged monkey model study
Abstract
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) Aβ 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 Aβ and Tau concentrations. Our results revealed that 7 consecutive days of 40-Hz auditory stimulation triggered a rapid and significant increase of Aβ levels by more than 200%, but no effect on Tau levels in the CSF. Additionally, we observed that the elevation of CSF Aβ 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 Aβ senile plaque pathology, whereas Tau pathology was negative or very weak. These results provide a good explanation for the differences between the CSF Aβ 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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Wenchao Wang
State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences
Rongyao Huang
State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences
Longbao Lv
State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences
Xia Ma
Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences
Zhenhui Li
Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences
Yuhua Zhang
Key Laboratory of Crop Integrated Pest Management in South China, Ministry of Agriculture, Department of Pesticide Science, College of Plant Protection, South China Agricultural University
Jing Wu
Shihao Wu
Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences
Jianglei Xu
State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences
Yingzhou Hu
State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences
Christoph W. Turck
State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences
Hao Li
Xintian Hu
State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences