{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:01:14Z","timestamp":1793325674876,"version":"4.5.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alzheimer\u2019s disease, a progressive neurodegenerative disorder, is marked by beta-amyloid plaque accumulation and cognitive decline. The limited efficacy and significant side effects of anti-amyloid monoclonal antibody therapies have prompted exploration into innovative treatments like focused ultrasound therapy. Focused ultrasound shows promise as a non-invasive technique for disrupting the blood\u2013brain barrier, potentially enhancing drug delivery directly to the brain and improving the penetration of existing therapeutic agents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This systematic review was conducted using PubMed and Embase databases, focusing on studies published in the last ten years that examined the use of low\u2013intensity focused ultrasound for blood\u2013brain barrier disruption in Alzheimer\u2019s disease. The search strategy encompassed terms related to Alzheimer\u2019s disease, focused ultrasound, and the blood\u2013brain barrier. Studies were selected based on predefined inclusion and exclusion criteria. The quality of included studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence framework.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve studies were analyzed, the results of which suggested that low intensity focused ultrasound when combined with microbubbles may safely and transiently disrupt the blood\u2013brain barrier. These studies, primarily early-phase and observational, highlight the potential feasibility of focused ultrasound in facilitating drug delivery to the brain for the treatment of Alzheimer\u2019s disease. Notably, one study reported positive impacts on cognitive tests, suggesting potential direct therapeutic effects of focused ultrasound beyond blood\u2013brain barrier disruption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of the included studies indicate the use of focused ultrasound in Alzheimer\u2019s disease treatment might be safe and effective in transiently opening the blood\u2013brain barrier. Although current evidence is promising, further research is needed to establish generalizability. Future studies should also aim to further elucidate the mechanisms of action of low-intensity focused ultrasound as well as microbubbles for blood\u2013brain barrier opening and explore potential clinical benefits beyond blood\u2013brain barrier opening such as impacts on cognitive outcomes. Future studies should also aim for greater participant diversity to ensure findings are applicable across the full spectrum of Alzheimer\u2019s disease patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1426075","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T04:59:59Z","timestamp":1722920399000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Focused ultrasound therapy for Alzheimer\u2019s disease: exploring the potential for targeted amyloid disaggregation"],"prefix":"10.3389","volume":"15","author":[{"given":"Kurt","family":"Scott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Klaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref1","unstructured":"2024"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"101339","DOI":"10.1016\/j.arr.2021.101339","article-title":"Effects of monoclonal antibodies against amyloid-\u03b2 on clinical and biomarker outcomes and adverse event risks: a systematic review and meta-analysis of phase III RCTs in Alzheimer\u2019s disease","volume":"68","author":"Avgerinos","year":"2021","journal-title":"Ageing Res Rev"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.14336\/AD.2021.0510","article-title":"The applications of focused ultrasound (FUS) in Alzheimer\u2019s disease treatment: a systematic review on both animal and human studies","volume":"12","author":"Liu","year":"2021","journal-title":"Aging Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1517\/17425247.2014.897693","article-title":"Drug delivery across the blood\u2013brain barrier using focused ultrasound","volume":"11","author":"Burgess","year":"2014","journal-title":"Expert Opin Drug Deliv"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s40035-022-00333-x","article-title":"Enhanced delivery of a low dose of aducanumab via FUS in 5\u00d7FAD mice, an AD model. 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