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Neurosci."],"abstract":"<jats:p>The amyloid-\u03b2 (A\u03b2) hypothesis implicates A\u03b2 protein accumulation in Alzheimer\u2019s disease (AD) onset and progression. However, therapies targeting A\u03b2 have proven insufficient in achieving disease reversal, prompting a shift to focus on early intervention and alternative therapeutic targets. Focused ultrasound (FUS) paired with systemically-introduced microbubbles (\u03bcB) is a non-invasive technique for targeted and transient blood\u2013brain barrier opening (BBBO), which has demonstrated A\u03b2 and tau reduction, as well as memory improvement in models of late-stage AD. However, similar to drug treatments for AD, this approach is not sufficient for complete reversal of advanced, symptomatic AD. Here we aim to determine whether early intervention with FUS-BBBO in asymptomatic AD could delay disease onset. Thus, the objective of this study is to measure the protective effects of FUS-BBBO on anxiety, memory and AD-associated protein levels in female and male triple transgenic (3xTg) AD mice treated at an early age and disease state. Here we show that early, repeated intervention with FUS-BBBO decreased anxiety-associated behaviors in the open field test by 463.02 and 37.42% in male and female cohorts, respectively. FUS-BBBO preserved female aptitude for learning in the active place avoidance paradigm, reducing the shock quadrant time by 30.03 and 31.01% in the final long-term and reversal learning trials, respectively. Finally, FUS-BBBO reduced hippocampal accumulation of A\u03b240, A\u03b242, and total tau in females by 12.54, 13.05, and 3.57%, respectively, and reduced total tau in males by 18.98%. This demonstration of both cognitive and pathological protection could offer a solution for carriers of AD-associated mutations as a safe, non-invasive technique to delay the onset of the cognitive and pathological effects of AD.<\/jats:p>","DOI":"10.3389\/fnins.2023.1229683","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T12:59:05Z","timestamp":1690462745000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Getting ahead of Alzheimer\u2019s disease: early intervention with focused ultrasound"],"prefix":"10.3389","volume":"17","author":[{"given":"Rebecca L.","family":"Noel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L.","family":"Gorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec J.","family":"Batts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa E.","family":"Konofagou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.1257","article-title":"Temporal and spatial strategies in an active place avoidance task on Carousel: a study of effects of stability of arena rotation speed in rats.","volume":"3","author":"Bahn\u00edk","year":"2015","journal-title":"PeerJ"},{"key":"B2","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/nrn2194","article-title":"Tau-mediated neurodegeneration in Alzheimer\u2019s disease and related disorders.","volume":"8","author":"Ballatore","year":"2007","journal-title":"Nat. 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