A comparative study of the effects of Aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease

Abstract Background Aducanumab is an anti-amyloid-? (A?) antibody that achieved reduced amyloid pathology in Alzheimer’s disease (AD) trials; however, it controversial whether also improved cognition, which has been suggested would require a sufficiently high cumulative dose of the brain. Therapeutic ultrasound, contrast, only begun to be investigated human AD clinical trials. We have previously shown scanning ultrasound combination with intravenously injected microbubbles (SUS), temporarily and safely opens blood-brain barrier (BBB), removes restores cognition APP23 mice. However, there no direct testing how effects SUS compare immunotherapy or therapy more effective. Methods In study comprising four treatment arms, we tested efficacy analog, Adu, both comparison SUS, as therapy, mice (aged 13–22 months), using sham control. The active place avoidance (APA) test was used spatial memory, histology ELISA were measure amyloid. Brain levels determined. Results found Adu total plaque area hippocampus additive effect observed (SUS + Adu). Whereas cortex where trend towards reducing from either yielded statistically significant decrease compared sham. Only groups included animals had their load below 1% above 10%. There robust improvement memory for group only, this level when measured 3 days post-treatment, 5-fold higher those received on its own. Together, these findings suggest should considered option AD. Alternatively, trial together increase brain may warranted.