{
  "abstract": "Background Contact sports, including rugby union, are associated with higher rates of neurodegenerative dementia, due to various underlying pathologies such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). 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.Methods 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).Results 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 (Aβ38), and increased phospho-tau 181 (p-tau181). 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.Conclusions 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- 181 more so than p-tau217 points towards non-AD tau pathology. Our findings motivate longitudinal characterisation, including comparison with other neurodegenerative diseases.",
  "authors": [
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "Neil Graham"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "Karl Zimmerman"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "Jessica Hain"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "Erin Rooney"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "Ying Lee"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "Martina del Giovane"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "Thomas Parker"
    },
    {
      "affiliations": [
        "Institute of Sport, Exercise and Health, UCL, London, England, UK"
      ],
      "name": "Mathew Wilson"
    },
    {
      "affiliations": [
        "Department of Stroke and Neuroscience, Imperial College London NHS Healthcare Trust, London, UK"
      ],
      "name": "Maneesh Patel"
    },
    {
      "affiliations": [
        "UK Dementia Research Institute, UCL, London, UK",
        "Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK"
      ],
      "name": "Elena Veleva"
    },
    {
      "affiliations": [
        "UK Dementia Research Institute, UCL, London, UK",
        "Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK"
      ],
      "name": "Owen Swann"
    },
    {
      "affiliations": [
        "UK Dementia Research Institute, UCL, London, UK",
        "Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK"
      ],
      "name": "Amanda J Heslegrave"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "Lucia M Li"
    },
    {
      "affiliations": [
        "UK Dementia Research Institute, UCL, London, UK",
        "Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK"
      ],
      "name": "Henrik Zetterberg"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK"
      ],
      "name": "Daniel Friedland"
    },
    {
      "affiliations": [
        "Institute of Sport, Exercise and Health, UCL, London, England, UK",
        "Acute Stroke and Brain Injury Unit, National Hospital for Neurology and Neurosurgery, London, London, UK"
      ],
      "name": "Richard Sylvester"
    },
    {
      "affiliations": [
        "Brain Sciences, Imperial College London, London, UK",
        "UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK"
      ],
      "name": "David Sharp"
    }
  ],
  "title": "Midlife plasma proteomic profiles indicate altered amyloid and tau processing in former elite rugby players",
  "uid": "f00a1e39-812a-55fa-beec-3800f6e9dfa3"
}