ArticleProceedings of the National Academy of Sciences of the United States of America2026
Long-term effects of forty-hertz auditory stimulation as a treatment of Alzheimer's disease: Insights from an aged monkey model study.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Gamma Oscillations, Sensory Stimulation, and Glymphatic Function: Toward User-Friendly Auditory Interventions for Brain Health in Aging and Neurodegeneration.Medical sciences (Basel, Switzerland) · 2026Review
- Screening the optimal rTSMS frequency to orchestrate immune-fibrotic remodeling for adult spinal cord repair.Frontiers in neuroscience · 2026Article
- Synaptic micromechanics and brain softening as a mechanobiological hypothesis for Alzheimer's disease.Frontiers in neuroscience · 2026Article
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13 authors.
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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.
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