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

Amyloid-beta (A beta) peptide has been implicated in the pathogenesis of Alzheimer's disease (AD). We present a non-pharmacological approach for removing A beta and restoring memory function in a mouse model of AD in which A beta is deposited in the brain. We used repeated scanning ultrasound (SUS) treatments of the mouse brain to remove A beta, without the need for any additional therapeutic agent such as anti-A beta antibody. Spinning disk confocal microscopy and high-resolution three-dimensional reconstruction revealed extensive internalization of A beta 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 A beta in the mouse brain without causing overt damage, and should be explored further as a noninvasive method with therapeutic potential in AD.