Preliminary evidence for the combined efficacy of focused ultrasound blood–brain barrier opening and Re-1 delivery for anxiety and memory improvement in a 3xTg-Alzheimer's disease mouse model

Abstract

The aim of this preliminary study is to evaluate the efficacy of early intervention with Focused Ultrasound-induced Blood–Brain Barrier Opening (FUS-BBBO) and Re-1 delivery for anxiety amelioration, memory improvement, and pathology reduction in an Alzheimer's Disease (AD) mouse model. FUS-BBBO was applied and Re-1 delivered to the hippocampi of presymptomatic, male triple transgenic (3xTg)-AD mice using a preventative paradigm of 10 total biweekly treatments over the course of 5 months. Following treatment, the animals underwent five days of behavioral testing for anxiety, spatial memory, and reversal learning. The combination of FUS-BBBO and Re-1 delivery showed evidence of improving the long-term spatial memory and short-term reversal learning with no significant effect on amyloid and tau accumulation. The small sample size is a limiting factor for this preliminary study, which still offers promising indications in support of early intervention with amyloid-targeting Re-1 and FUS-BBBO for cognitive and minor pathological improvement in AD.