{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:01Z","timestamp":1787028541844,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Auckland University of Technology"},{"name":"Durham University (UK)"},{"name":"Saudi Arabian Scholarship fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The health and well-being of retired rugby union and league players, particularly regarding the long-term effects of concussions, are of major concern. Concussion has been identified as a major risk factor for neurodegenerative diseases, such as Alzheimer\u2019s and Amyotrophic Lateral Sclerosis (ALS), in athletes engaged in contact sports. This study aimed to assess differences in specific biomarkers between UK-based retired rugby players with a history of concussion and a non-contact sports group, focusing on biomarkers associated with Alzheimer\u2019s, ALS, and CTE. We randomly selected a sample of male retired rugby or non-contact sport athletes (n = 56). The mean age was 41.84 \u00b1 6.44, and the mean years since retirement from the sport was 7.76 \u00b1 6.69 for participants with a history of substantial concussions (&gt;5 concussions in their career) (n = 30). The mean age was 45.75 \u00b1 11.52, and the mean years since retirement was 6.75 \u00b1 4.64 for the healthy controls (n = 26). Serum biomarkers (t-tau, RBP-4, SAA, Nf-L, and retinol), plasma cytokines, and biomarkers associated with serum-derived exosomes (A\u03b242, p-tau181, p-tau217, and p-tau231) were analyzed using validated commercial ELISA assays. The results of the selected biomarkers were compared between the two groups. Biomarkers including t-tau and p-tau181 were significantly elevated in the history of the substantial concussion group compared to the non-contact sports group (t-tau: p &lt; 0.01; p-tau181: p &lt; 0.05). Although between-group differences in p-tau217, p-tau231, SAA, Nf-L, retinol, and A\u03b242 were not significantly different, there was a trend for higher levels of A\u03b242, p-tau217, and p-tau231 in the concussed group. Interestingly, the serum-derived exosome sizes were significantly larger (p &lt; 0.01), and serum RBP-4 levels were significantly reduced (p &lt; 0.05) in the highly concussed group. These findings indicate that retired athletes with a history of multiple concussions during their careers have altered serum measurements of exosome size, t-tau, p-tau181, and RBP-4. These biomarkers should be explored further for the prediction of future neurodegenerative outcomes, including ALS, in those with a history of concussion.<\/jats:p>","DOI":"10.3390\/ijms25147811","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T16:35:58Z","timestamp":1721234158000},"page":"7811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Concussion-Related Biomarker Variations in Retired Rugby Players and Implications for Neurodegenerative Disease Risk: The UK Rugby Health Study"],"prefix":"10.3390","volume":"25","author":[{"given":"Norah","family":"Alanazi","sequence":"first","affiliation":[{"name":"Department of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham DH1 3LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-8179","authenticated-orcid":false,"given":"Melinda","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"},{"name":"Perron Institute for Neurological and Translational Sciences, Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1847-8128","authenticated-orcid":false,"given":"Patria","family":"Hume","sequence":"additional","affiliation":[{"name":"Sports Performance Research Institute New Zealand (SPRINZ), Faculty of Health and Environmental Science, Auckland University of Technology, AUT Millennium, 17 Antares Place, Mairangi Bay, Private Bag 92006, Auckland 1142, New Zealand"},{"name":"Traumatic Brain Injury Network (TBIN), Auckland University of Technology, Private Bag 92006, Auckland 1142, New Zealand"},{"name":"Auckland Bioengineering Institute, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"},{"name":"Technology and Policy Laboratory, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2179-2209","authenticated-orcid":false,"given":"Sarah","family":"Hellewell","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"},{"name":"Perron Institute for Neurological and Translational Sciences, Nedlands, WA 6009, Australia"},{"name":"Centre for Neuromuscular & Neurological Disorders, University of Western Australia, Crawley, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Horncastle","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham DH1 3LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0618-3173","authenticated-orcid":false,"given":"Chidozie","family":"Anyaegbu","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"},{"name":"Perron Institute for Neurological and Translational Sciences, Nedlands, WA 6009, Australia"},{"name":"Centre for Neuromuscular & Neurological Disorders, University of Western Australia, Crawley, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1475-0641","authenticated-orcid":false,"given":"Melissa G.","family":"Papini","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"},{"name":"Perron Institute for Neurological and Translational Sciences, Nedlands, WA 6009, Australia"},{"name":"Centre for Neuromuscular & Neurological Disorders, University of Western Australia, Crawley, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Hargreaves","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham DH1 3LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Halicki","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham DH1 3LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2686-8556","authenticated-orcid":false,"given":"Ian","family":"Entwistle","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham DH1 3LE, UK"},{"name":"Wolfson Research Institute for Health and Wellbeing, Durham University, Durham TS17 6BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Hind","sequence":"additional","affiliation":[{"name":"Wolfson Research Institute for Health and Wellbeing, Durham University, Durham TS17 6BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5453-0379","authenticated-orcid":false,"given":"Paul","family":"Chazot","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham DH1 3LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1007\/s40279-020-01310-y","article-title":"Cumulative sport-related injuries and longer term impact in retired male Elite-and 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