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Transl. Med."],"published-print":{"date-parts":[[2026,3,18]]},"abstract":"<jats:p>\n                    Cerebrovascular disruption has been implicated in the pathophysiology of head trauma and chronic traumatic encephalopathy (CTE). However, the long-term consequences of repetitive head trauma on blood-brain barrier (BBB) integrity and its link to cognitive function remain unknown. Here, using dynamic contrast\u2013enhanced magnetic resonance imaging (DCE-MRI), we show that BBB disruption can be detected years after the retirement of combat and collision sports athletes (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 47) from their respective sports. A subgroup of individuals (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 17) with extensive BBB disruption displayed worse cognitive decline compared with those with less extensive BBB disruption. Commonly used systemic markers of central nervous system injury and neurodegeneration were of limited utility; however, a greater systemic inflammatory burden with a higher proportion of circulating monocytes was associated with cognitive decline in the retired athletes. Transcriptomic analysis of these peripheral immune cells revealed dysregulation of the complement system and vascular developmental pathways. Altered expression of complement receptors, including\n                    <jats:italic toggle=\"yes\">C5AR1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">ITGAM<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">ITGB2<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">CD59<\/jats:italic>\n                    , a potent inhibitor of the membrane attack complex (MAC), was associated with BBB disruption and cognitive decline. Postmortem brain tissues from those with confirmed cases of CTE showed MAC deposition around cerebral blood vessels. Bioinformatic analysis of single-nucleus RNA sequencing data from postmortem individuals with CTE revealed microglia-endothelial cross-talk, which may mediate complement dysregulation. Together, our data suggest that sustained systemic inflammation and persistent BBB disruption are associated with the long-term outcome of repetitive head trauma.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adu6037","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:58:36Z","timestamp":1773856716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":13,"title":["Blood-brain barrier disruption, traumatic encephalopathy, and cognitive decline in retired athletes"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4192-9433","authenticated-orcid":true,"given":"Chris","family":"Greene","sequence":"first","affiliation":[{"name":"Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland."},{"name":"FutureNeuro Research Ireland Centre, Department of Physiology &amp; Medical Physics, RCSI University of Medicine and Health Sciences, 123 St. Stephen\u2019s Green, Dublin 2, Ireland."},{"name":"Department of Physiology &amp; Medical Physics, RCSI University of Medicine and Health Sciences, 123 St. Stephen\u2019s Green, Dublin 2, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Declan","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Health Care Centre, St. James\u2019s Hospital, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2608-9771","authenticated-orcid":true,"given":"Sheida","family":"Mirloo","sequence":"additional","affiliation":[{"name":"Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3128-8097","authenticated-orcid":true,"given":"Ruairi","family":"Connolly","sequence":"additional","affiliation":[{"name":"Department of Neurology, Health Care Centre, St. James\u2019s Hospital, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8818-4331","authenticated-orcid":true,"given":"Jeffrey","family":"O\u2019Callaghan","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-1773","authenticated-orcid":true,"given":"Avril","family":"Reddy","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2005-6661","authenticated-orcid":true,"given":"Jeff","family":"Henderson","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-0479","authenticated-orcid":true,"given":"Gerg\u0151","family":"Porkol\u00e1b","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland."},{"name":"FutureNeuro Research Ireland Centre, Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-801X","authenticated-orcid":true,"given":"Adam","family":"McGlinchey","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1451-3803","authenticated-orcid":true,"given":"Nicole","family":"Hanley","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-4142","authenticated-orcid":true,"given":"Siobhan","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Health Care Centre, St. James\u2019s Hospital, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F. 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