Therapeutic Ultrasound as a Treatment Modality for Physiological and Pathological Ageing Including Alzheimer's...

Physiological and pathological ageing (as exemplified by Alzheimer's disease, AD) are characterized by a progressive decline that also includes cognition. How this decline can be slowed or even reversed is a critical question. Here, we discuss therapeutic ultrasound as a novel modality to achieve this goal. In our studies, we explored three fundamental strategies, (i) scanning ultrasound on its own (SUS^only), (ii) therapeutic ultrasound in concert with intravenously injected microbubbles (which transiently opens the blood-brain barrier, SUS^+MB), and (iii) SUS^+MB in combination with therapeutic antibodies (SUS^+MB+mAb). These studies show SUS^+MB effectively clears amyloid and restores memory in amyloid-depositing mice and partially clears Tau and ameliorates memory impairments in Tau transgenic mice, with additional improvements found in combination trials (SUS^+MB+mAb). Interestingly, both SUS^only and SUS^+MB restored the induction of long-term potentiation (LTP, electrophysiological correlate of memory) in senescent wild-type mice. Both lead to increased neurogenesis, and SUS^only, in particular, resulted in improved spatial memory. We discuss these findings side-by-side with our findings obtained in AD mouse models. We conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may present a treatment option not only for AD but also for enhancing cognition in physiological ageing.