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Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to reversibly disrupt the BBB. However, treatment of diffuse regions across the brain along with the effect on Alzheimer\u2019s disease relevant pathology need to be better characterized. This study is an open-labelled single-arm trial (NCT03739905) to investigate the feasibility of modulating BBB permeability in the default mode network and the impact on cognition, amyloid and tau pathology as well as BBB integrity. Nine participants [mean age 70.2 \u00b1 7.2 years, mean Mini-Mental State Examination (MMSE) 21.9] underwent three biweekly procedures with follow-up visits up to 6 months. The BBB permeability of the bilateral hippocampi, anterior cingulate cortex and precuneus was transiently increased without grade 3 or higher adverse events. Participants did not experience worsening trajectory of cognitive decline (ADAS-cog11, MMSE). Whole brain vertex-based analysis of the 18F-florbetaben PET imaging demonstrated clusters of modest SUVR reduction in the right parahippocampal and inferior temporal lobe. However, CSF and blood biomarkers did not demonstrate any amelioration of Alzheimer\u2019s disease pathology (P-tau181, amyloid-\u03b242\/40 ratio), nor did it show persistent BBB dysfunction (plasma PDGFRbeta and CSF-to-plasma albumin ratio). This study provides neuroimaging and fluid biomarker data to characterize the safety profile of MRgFUS BBB modulation in neurodegeneration as a potential strategy for enhanced therapeutic delivery.<\/jats:p>","DOI":"10.1093\/brain\/awac459","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T10:25:58Z","timestamp":1670840758000},"page":"865-872","source":"Crossref","is-referenced-by-count":85,"title":["Blood\u2013brain barrier opening of the default mode network in Alzheimer\u2019s disease with magnetic resonance-guided focused ultrasound"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-2404","authenticated-orcid":false,"given":"Ying","family":"Meng","sequence":"first","affiliation":[{"name":"Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , Canada"},{"name":"Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maged","family":"Goubran","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , Canada"},{"name":"Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , Canada"},{"name":"Department of Medical Biophysics, University of Toronto , Toronto, ON M5G 1L7 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4754-2221","authenticated-orcid":false,"given":"Jennifer S","family":"Rabin","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , Canada"},{"name":"Hurvitz Brain Sciences Research Program, Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , Canada"},{"name":"Rehabilitation Sciences Institute, University of Toronto , Toronto, ON M5G 1V7 , Canada"},{"name":"Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto , Toronto, ON M4N 3M5 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"McSweeney","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9879-7497","authenticated-orcid":false,"given":"Julie","family":"Ottoy","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, ON M4N 3M5 , 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, London W1T 7NF , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg , 405 30 M\u00f6lndal , Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg , 405 30 Gothenburg , Sweden"},{"name":"King\u2019s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute , London SE5 9RX , UK"},{"name":"NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation , London SE5 8AF , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-4358","authenticated-orcid":false,"given":"Thomas K","family":"Karikari","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg , 405 30 M\u00f6lndal , Sweden"},{"name":"Department of Psychiatry, School of Medicine, University of Pittsburgh , Pittsburgh, PA 15213 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg , 405 30 M\u00f6lndal , Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , 413 45 M\u00f6lndal , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E","family":"Black","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of 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