Focused ultrasound and Alzheimer's disease A systematic review.
Authors: Souza RMDCE, da Silva ICS, Delgado ABT, da Silva PHV, Costa VRX
Alzheimer's disease (AD) affects millions of people, however, there is still no effective treatment. The use of focused ultrasound with microbubbles (FUS-MB) for the opening of the blood-brain barrier has been recently studied and may become a promising therapeutic target. To discuss the use of FUS-MB for the treatment of AD and to present some of the techniques used. A systematic review was performed of MEDLINE/PubMed and Biblioteca Virtual em Saúde (BVS) services, using the keywords: focused ultrasound, Alzheimer, amyloid-b. Original articles were included in the study; studies that did not focus on Alzheimer's treatment were excluded. Fifteen original studies were selected. Preclinical trials were able to reduce amyloid-b plaques and tau phosphorylation, improving cognitive performance in AD animals. The results are very promising, but the therapy still requires maturation. Further studies are needed to systematize all the techniques used and their effects in order to enable use in humans.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To review and discuss the use of focused ultrasound with microbubbles (FUS-MB) as a treatment for Alzheimer's disease and to present the techniques used.
Disease model
Alzheimer's disease
Outcomes and Safety
Summary of Outcomes
FUS with microbubbles in preclinical AD models reduced amyloid‑β plaques and tau phosphorylation, activated glia, increased hippocampal neurogenesis/plasticity and improved spatial memory and cognitive performance while enabling BBB delivery of antibodies/drugs. Reported successful parameters included frequencies mostly 1–2 MHz (one study 0.588 MHz), sonication times commonly ~120 s, microbubble doses ~0.02–0.04 ml/kg, acoustic pressures tuned to frequency and bubble size, repeated (e.g. weekly) hippocampal sonication, MRgFUS guidance, and use of overlapping foci for larger-volume openings.
Duration of biological effect
4 days
Safety-related matter
Preclinical studies described FUS‑MB as transient, targeted and generally safe (well tolerated in animal models, with some groups reporting larger‑volume openings can be performed safely), and a small human study (n=5) reported no moderate or severe adverse effects with BBB closure within 24 hours. However, safety evidence is limited: some reports noted longer BBB closure times (3–5 days) and inadvertent passage of agents to adjacent brain regions, so larger human trials are needed to fully assess risks.
Brain Region
Ultrasound Parameters
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
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