New Insights into How TPS Enhances Brain Function in Alzheimer’s Mouse Models
A new milestone in TPS research for Alzheimer’s has been achieved! For the first time, scientists have conducted a detailed animal study on healthy and transgenic mice with Alzheimer’s to explore the effects of Transcranial Pulse Stimulation (TPS). This study, a collaborative effort between ETH Zurich and University of Zurich, funded by InnoSuisse, investigated how TPS influences both brain structure and blood flow. The results, published in the prestigious journal Alzheimer & Dementia, are exciting: not only did TPS improve microcirculation in the brain, but it also demonstrated a high level of safety by maintaining the integrity of the blood-brain barrier (BBB) even at higher energy levels.
This pioneering study marks the first detailed exploration of TPS in Alzheimer’s disease animal models, providing crucial insights into its underlying mechanisms. It also represents the initial publication in a series of forthcoming research from the group, aimed at deepening our understanding of how TPS influences the AD brain.
What is Transcranial Pulse Stimulation (TPS)?
TPS is a non-invasive brain stimulation technique (NIBS) that uses very short acoustic pulses to create mechanical effects in targeted brain areas. Unlike methods that rely on continuous ultrasound waves, these short pulses do not generate heat, making TPS a safe treatment option.1,2,3
Preclinical studies in rats have shown that TPS is safe, and clinical trials showing improvements in cognitive performance and depression symptoms.2,4 However, understanding exactly how TPS influences brain activity and vascular function is crucial for potentially optimizing its therapeutic use in patients.
Key Findings from the Study
Enhanced Blood Flow in the Brain
The researchers observed a significant increase in blood volume within the brain’s microvascular network following TPS treatment. Using real-time optoacoustic (OA) imaging, they monitored blood flow during and after TPS sessions, finding consistent improvements in circulation in both healthy and AD mice.
Safety at Higher Energy Levels
An essential question for TPS research is whether higher energy levels can cause damage to the brain, particularly by disrupting the blood-brain barrier BBB. This study addressed this concern by applying energy densities in the brain five times higher than in humans. The integrity of the BBB was confirmed through multiple methods, including contrast-enhanced MRI and histological staining, with no evidence of leakage or damage observed.
Different Stimulation Requirements in Alzheimer’s Mice
The study found that while TPS enhanced blood flow in both healthy and Alzheimer’s mice, the latter required higher energy levels to achieve similar effects. This suggests that the pathological changes in blood vessels caused by Alzheimer’s disease reduce their responsiveness to stimulation. The results suggest that future clinical applications of TPS may need to be personalized, with energy levels adjusted based on the patient’s cerebrovascular condition.
What’s Next?
This publication is the first in a series of planned studies by the research group. Future research will focus on long-term outcomes of TPS in healthy and Alzheimer’s models, including its effects on neuronal activity and cognitive behaviour. The current findings pave the way for further understanding and optimization for clinical application of TPS in Patients with Alzheimer’s disease.
Want to learn more? Read the full study in the journal Alzheimer & Dementia: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14511
1Truong DQ, Thomas C, Hampstead BM, Datta A. Comparison of transcranial focused ultrasound and transcranial pulse stimulation for neuromodulation: a computational study. Neuromodulation. 2022;25:606-
613.
2R Beisteiner, E Matt, C Fan, et al. Transcranial pulse stimulation with ultrasound in Alzheimer’s disease—a new navigated focal brain therapy. Adv Sci. 2020;7:1902583.
3Chen X, You J,Ma H, Zhou M, Huang C. Transcranial pulse stimulation in Alzheimer’s disease. CNS Neurosci Ther. 2024;30:e14372.
4GT Shinzato, T Assone, PC Sandler, et al. Non-invasive sound wave brain stimulation with transcranial pulse stimulation (TPS) improves neuropsychiatric symptoms in Alzheimer’s disease. Brain Stimulation. 2024;17:413-415.
