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New ultrasensitive multiplexed immunoassays may clarify disease mechanisms after repetitive head impacts (RHI) and traumatic brain injury, potentially aiding risk-stratification, early diagnosis and dementia treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Midlife participants in the ABHC cohort underwent plasma biomarker quantification (NULISA - NUcleic acid Linked Immuno-Sandwich Assay; n=124 markers), 3T MRI, trauma exposure ascertainment and phenotyping. Regressions quantified exposure-specific protein expression, relationship to trauma (including position) and brain atrophy, using cluster analysis to test correlates of traumatic encephalopathy syndrome (TES).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      197 former elite rugby players and 33 controls were assessed. 24 (12.2%) met criteria for TES but none had dementia. Ex-players returned reduced plasma glial fibrillary acidic protein (GFAP), kallikrein-6 (KLK6) and synaptosomal-associated protein 25 (SNAP25). Ex-forwards specifically showed reduced plasma beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), amyloid beta-38 (A\u03b238), and increased phospho-tau\n                      <jats:sub>181<\/jats:sub>\n                      (p-tau\n                      <jats:sub>181<\/jats:sub>\n                      ). KLK6 was lower in ex-backs than controls. No biomarkers related to career duration, concussion load or regional brain volume, nor did clustering relate to TES.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Ex-players showed distinctive plasma biomarker changes, more prominently in ex-forwards, possibly reflecting greater RHI exposure. Plasma KLK6, an endothelial serine protease, was reduced across the ex-player group, with potential diagnostic or prognostic utility in future. Reduced GFAP and SNAP25 in ex-forwards has an uncertain basis, while elevated p-tau-\n                      <jats:sub>181<\/jats:sub>\n                      more so than p-tau\n                      <jats:sub>217<\/jats:sub>\n                      points towards non-AD tau pathology. Our findings motivate longitudinal characterisation, including comparison with other neurodegenerative diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2025-336593","type":"journal-article","created":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T17:20:47Z","timestamp":1759684847000},"page":"393-397","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Midlife plasma proteomic profiles indicate altered amyloid and tau processing in former elite rugby players"],"prefix":"10.1136","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0183-3368","authenticated-orcid":false,"given":"Neil","family":"Graham","sequence":"first","affiliation":[{"name":"Brain Sciences, Imperial College London, London, UK"},{"name":"UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, 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