A wearable spatiotemporal controllable ultrasonic device with amyloid-β disaggregation for continuous Alzheimer's disease therapy.

The rising prevalence of Alzheimer's disease (AD) due to an aging population has made the search for effective treatments more urgent than ever. Previous studies have demonstrated that continuous ultrasound can depolymerize amyloid proteins, offering potential relief from AD. In this study, we present a portable, fully integrated wearable ultrasound system designed to promote amyloid protein depolymerization. The system comprises a flexible honeycomb ultrasonic array patch, a flexible printed circuit, and an interactive terminal control system to facilitate the treatment process. Our results demonstrate that the system effectively reduces amyloid proteins in the brain, improves cognitive function in a familial Alzheimer's disease (FAD) mouse model, enhances microglial phagocytosis of amyloid-β plaques, and shifts microglia polarization from M1 to M2. These changes contribute to a mitigated inflammatory environment in the brain. This innovative approach may pave the way for noninvasive, personalized treatments for AD, potentially transforming therapeutic strategies in neurodegenerative disorders.