Print This PostAs I write this, excitement is building around the world ahead of today’s 2026 World Cup final. Over the past few weeks, we have shared in the joy, drama and unpredictability of the beautiful game. Yet football’s history also has a darker side – and one that we, as dementia researchers, are uniquely placed to address.
Several members of England’s celebrated 1966 World Cup-winning squad died from dementia, these include Nobby Stiles, Martin Peters and Ray Wilson. It is believed that chronic traumatic encephalopathy (CTE) or other dementia are likely to have resulted from repetitive head trauma sustained during play. Among the most poignant cases is that of Jeff Astle, the West Bromwich Albion striker renowned for his heading ability, who died aged 59 from a neurodegenerative disease subsequently attributed to CTE. A coroner recorded a verdict of industrial disease.
CTE was brought to wider scientific prominence by Nigerian-American pathologist Dr Bennet Omalu, whose landmark 2005 paper described the condition in a former NFL player, a story later dramatised in the film Concussion, with Will Smith in the lead role. CTE has since been confirmed at post-mortem in individuals across a wide range of sports including association football, rugby, boxing and wrestling, all of which carry the potential for repetitive head injury, as well as in military veterans and survivors of domestic abuse. In a landmark 2023 case, Australian rules footballer Heather Anderson became the first professional sportswoman to receive a confirmed CTE diagnosis. She was 28 when she died and had endured one recorded head injury.
CTE is now understood to be a condition distinct from Alzheimer’s disease, though the two share important pathological features.
It is classified primarily as a tauopathy, in which both 3-repeat and 4-repeat isoforms of tau protein are deposited initially in the cerebral cortex, characteristically at the depths of the sulci in the superficial neocortical layers II and III. This perivascular pattern is not seen in Alzheimer’s disease. Following brain injury, particularly diffuse axonal injury, tau aggregation progresses rapidly and spreads unevenly across the cortex. Amyloid-beta deposition is usually less prominent or absent in CTE, further distinguishing it from Alzheimer’s pathology, while TDP-43 inclusions are more frequently observed in CTE brains than in Alzheimer’s disease. Cryo-electron microscopy has revealed that tau filaments extracted from CTE and Alzheimer’s brains share similar but non-identical conformations, with overlapping hyperphosphorylation patterns. At a neuroimaging level, CTE is associated with atrophy of the cavum septum pellucidum and enlargement of the lateral and third ventricles, a pattern that differs from the medial temporal lobe atrophy more typically observed in Alzheimer’s disease.
Early diagnosis is essential if emerging therapies are to have any meaningful impact. As with other neurodegenerative diseases, however, prevention remains the most powerful tool available. The concept of traumatic encephalopathy syndrome (TES) offers a clinical framework for identifying individuals at risk for CTE during life. Diagnostic criteria include a history of repetitive head injury with persistent symptoms lasting over a year, alongside progressive mood impairment and cognitive decline. Since CTE has historically been diagnosable only at post-mortem, the search for distinctive in-life biomarkers has become a research priority. In 2025, the Leon Thal Summit convened an international panel of clinicians, neuroscientists, to evaluate the current state of biomarkers for CTE. Advances in tau-specific PET imaging are increasing the potential for ante-mortem diagnosis, enabling the characteristic CTE pattern of tau deposition to be visualised in living individuals. Studies have shown that total tau rises in the serum following head trauma and returns towards baseline in those who recover well. Crucially, recent work has identified p-tau231 as a promising marker capable of distinguishing CTE from Alzheimer’s disease, a distinction that could be used alongside brain imaging and longitudinal monitoring of TES progression to support diagnosis during life.
On the therapeutic front, progress made against other tauopathies is increasingly relevant to CTE. Antisense oligonucleotides (ASOs), which have already transformed treatment in CAG-repeat diseases such as Huntington’s disease, are now being tested for their ability to silence MAPT mRNA and reduce tau expression in Alzheimer’s disease and progressive supranuclear palsy, with potential applicability to CTE. Monoclonal antibodies targeting tau through both active and passive immunotherapy approaches are yielding encouraging results in Phase 2 clinical trials, while tau aggregation inhibitors represent a further strategy for slowing pathological deposition, reducing brain atrophy and preserving cognitive function. Given that CTE frequently occurs alongside other co-pathologies, these multi-target approaches may prove particularly relevant.
Ultimately, prevention is the most transformative strategy available. Rule changes in sport may hold the greatest promise for protecting the brains of future generations. In the UK, a phased ban on heading the ball in youth football matches is being introduced between 2024 and 2027, while the United States banned heading for players under 11 as long ago as 2015. In rugby, World Rugby’s lower tackle height trials, now adopted by over ten nations at community level, have produced concussion reductions of up to 30% in some settings. In the NFL, the redesigned Dynamic Kick-off rule reduced concussions on kick-offs by 43% in its first season. More broadly, a joint concussion awareness campaign launched in 2024 by the World Health Organisation and FIFA is helping to embed a culture in which full recovery before return to play is treated as non-negotiable.
As we enjoy the beautiful game, let us commit to looking after those beautiful brains.
Professor Louise Serpell
Author
Professor Louise Serpell is an Emerita Professor of Biochemistry at the University of Sussex. Her research focuses on how proteins misfold and form amyloid structures linked to Alzheimer’s disease and other neurodegenerative conditions, using approaches from structural biology and molecular biophysics. Louise completed her DPhil at the University of Oxford and later established her own research group in the UK. Alongside her research career, she has been active in mentoring, public engagement, and supporting early career researchers.
Alzheimer's Association
Professor Louise Serpell
Dementia Researcher
