Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model

Repeated scanning ultrasound in the absence of a therapeutic agent removes amyloid-β and restores memory in an Alzheimer’s disease mouse model. Can ultrasound restore memory? Transgenic mice with increased amyloid-β (Aβ) production show several aspects of Alzheimer’s disease, including Aβ deposition and memory impairment. By repeatedly treating these Aβ-forming mice with scanning ultrasound, Leinenga and Götz now demonstrate that Aβ is removed and memory is restored as revealed by improvement in three memory tasks. These improvements were achieved without the use of any therapeutic agent, and the scanning ultrasound treatment did not induce any apparent damage to the mouse brain. The authors then showed that scanning ultrasound activated resident microglial cells that took up Aβ into their lysosomes. These findings suggest that repeated scanning ultrasound may be a noninvasive method with potential for treating Alzheimer’s disease. Amyloid-β (Aβ) peptide has been implicated in the pathogenesis of Alzheimer’s disease (AD). We present a nonpharmacological approach for removing Aβ and restoring memory function in a mouse model of AD in which Aβ is deposited in the brain. We used repeated scanning ultrasound (SUS) treatments of the mouse brain to remove Aβ, without the need for any additional therapeutic agent such as anti-Aβ antibody. Spinning disk confocal microscopy and high-resolution three-dimensional reconstruction revealed extensive internalization of Aβ into the lysosomes of activated microglia in mouse brains subjected to SUS, with no concomitant increase observed in the number of microglia. Plaque burden was reduced in SUS-treated AD mice compared to sham-treated animals, and cleared plaques were observed in 75% of SUS-treated mice. Treated AD mice also displayed improved performance on three memory tasks: the Y-maze, the novel object recognition test, and the active place avoidance task. Our findings suggest that repeated SUS is useful for removing Aβ in the mouse brain without causing overt damage, and should be explored further as a noninvasive method with therapeutic potential in AD.