A comprehensive review of advanced focused ultrasound (FUS) microbubbles-mediated treatment of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive neurodegeneration, memory loss, and cognitive impairment leading to dementia and death. The blood-brain barrier (BBB) prevents the delivery of drugs into the brain, which can limit their therapeutic potential in the treatment of AD. Therefore, there is a need to develop new approaches to bypass the BBB for appropriate treatment of AD. Recently, focused ultrasound (FUS) has been shown to disrupt the BBB, allowing therapeutic agents to penetrate the brain. In addition, microbubbles (MBs) as lipophilic carriers can penetrate across the BBB and deliver the active drug into the brain tissue. Therefore, combined with FUS, the drug-encapsulated MBs can pass through the ultrasound-disrupted zone of the BBB and diffuse into the brain tissue. This review provides clear and concise statements on the recent advances of the various FUS-mediated MBs-based carriers developed for delivering AD-related drugs. In addition, the sonogenetics-based FUS/MBs approaches for the treatment of AD are highlighted. The future perspectives and challenges of ultrasound-based MBs drug delivery in AD are then discussed.