Key Points
- This article provides a preclinical and clinical overview of using low-intensity ultrasound plus microbubbles to disrupt the blood-brain barrier for the delivery of immunotherapies in Alzheimer’s disease.
- It then compares in vitro and in vivo models, strategies for combining therapeutic agents with microbubbles, and techniques to understand observable bioeffects.
- The authors discuss questions on how in vitro studies can be translated to animal and human applications.
In this review article, Jürgen Götz, PhD, and his team at Queensland Brain Institute first provide an overview of preclinical and clinical trials that have used low-intensity ultrasound plus microbubbles to disrupt the blood-brain barrier (BBB) for the delivery of immunotherapies in Alzheimer’s disease. The immunotherapies described are those that target either amyloid-beta peptides or tau proteins. The article then compares various models for in vitro BBB studies, strategies for combining therapeutic agents with microbubbles, and the impact of super-resolution microscopy on the field. In vitro BBB models may be cellular, two-dimensional, or three-dimensional, and there are many molecular imaging techniques that can be used to understand the bioeffects that occur during these types of experiments. To conclude, the group discusses several treatment development and optimization questions on how in vitro studies can be translated to animal and human applications.