Combining low-dose radiation therapy and magnetic resonance guided focused ultrasound to reduce Amyloid-β deposition in Alzheimer's Disease

Amyloid-β deposition is one of the neuropathological hallmarks of Alzheimer's disease (AD), but pharmacological strategies toward its reduction are poorly effective.Preclinical studies indicate that low-dose radiation therapy (LD-RT) may reduce brain amyloid-β. Animal models and proof-of-concept preliminary data in humans have shown that magnetic resonance guided focused ultrasound (MRgFUS) can reversibly open the blood-brain-barrier and facilitate the delivery of targeted therapeutics to the hippocampus, to reduce amyloid-β and promote neurogenesis in AD. Ongoing clinical trials on AD are exploring whole-brain LD-RT, which may damage radio-sensitive structures, i.e., hippocampus and white matter, thus contributing to reduced neurogenesis and radiation-induced cognitive decline. However, selective irradiation of cortical amyloid-β plaques through advanced LD-RT techniques might spare the hippocampus and white matter. We propose combined use of advanced LD-RT and targeted drug delivery through MRgFUS for future clinical trials to reduce amyloid-β deposition in AD since its preclinical stages.