Multiple concussions in rugby players linked to higher levels of proteins linked to neurodegenerative diseases

A new study has found that retired rugby players who have suffered multiple concussions have higher levels of certain proteins in their blood, which could make them more susceptible to diseases such as motor neurone disease (MND).

The research, led by Durham University, shows that it is possible to measure specific key biomarkers that can indicate disease or predict possible future disease in the blood of athletes who have suffered multiple head trauma.

This is the first study to investigate a range of specific biomarkers as part of the UK Rugby Health project.

If athletes’ blood can be tested and monitored for these specific proteins, we may be able to diagnose neurodegenerative diseases early and intervene in time.

The study was published in the International Journal of Molecular Sciences.

The retired male rugby players who participated had a significant history of concussions during their playing careers. Their blood samples contained more indicators of nerve damage, known as serum exosomes, compared to a control group of fellow athletes who had not suffered head trauma.

Researchers found higher levels of specific proteins called serum t-tau and tau-p181, which play a crucial role in the development of Alzheimer’s and ALS, compared to healthy controls.

They also found that rugby players who had suffered a concussion during their careers had lower levels of a retinoid transporter protein called RBP-4, which plays an important role in brain development and function. The researchers suggest that this could be a reason for the development of retinoid-based drugs.

They strongly recommend that contact athletes be monitored after they stop playing, especially if they have suffered a concussion.

In recent years, much effort has been put into developing blood biomarkers that could potentially aid in the early diagnosis and monitoring of neurodegenerative diseases such as Alzheimer’s.

Lead author of the study, Professor Paul Chazot from Durham University’s Department of Biosciences, said: “The long-term effects of concussion on rugby players, footballers, boxers and retired military personnel are of significant concern, due to links with neurodegenerative diseases.

“This study provides us with the impetus for a biomarker toolbox that will allow us to periodically monitor the brain health of retired contact athletes, particularly those who have sustained a concussion during their career.

“It will also pave the way for the introduction of the necessary interventions to minimize the development of future neurodegenerative diseases. We have a range of interventions that are currently in advanced stages of development.”

Because the interventions must first be tested in clinical trials, it could take several years before they are available, the researchers emphasize.

Co-author Dr Karen Hind, Honorary Fellow at the Wolfson Research Institute for Health and Wellbeing at Durham University, initiated the UK Rugby Health study. She added: “This is a crucial development in the field and we call for continued efforts to define the pathways leading to concussion-induced neurodegenerative diseases.

Alix Popham, who was not involved in the research, is a retired international rugby player. He played 33 caps for Wales, including two World Cups and winning a Six Nations Grand Slam. Alix retired in 2011 and was diagnosed in April 2020 with probable chronic traumatic encephalopathy (CTE) and early-onset dementia as a result of a traumatic brain injury he sustained during his rugby career. He is a co-founder of the charity Head for Change.

He said: “This is further evidence that major changes are needed to protect current rugby players. World Rugby must pull their heads out of the sand and in turn protect the sport.”

The study analyzed blood samples from 56 male professional athletes seven years after they retired from their sport. This included 30 retired rugby players who had suffered more than five concussions in their active careers. They were compared with 26 retired rugby players without concussions and retired athletes from non-contact sports.

The researchers are now seeking urgent funding to conduct a follow-up study with the players. This will provide a clearer picture of the current levels of the relevant proteins in the players’ blood, including any changes, their current health status and potential health outcomes.

The biomarkers included were total tau (t-tau), three forms of phosphorylated tau (p-tau), serum amyloid alpha (SAA), beta-amyloid (Aβ42), retinol-binding protein 4 (RBP-4), retinol and neurofilament light (Nf-L), and exosome size.

The research was conducted by Durham University with contributions from researchers at Curtin University (Australia), the University of Western Australia (Australia), Auckland University of Technology (New Zealand) and the University of Auckland (New Zealand).

This latest study is the first from the UK Rugby Health Project to look at biomarkers. The project was established in 2016 as an extension of the 2012 New Zealand Rugby Health Project.

This research builds on previous studies showing a significant association between the number of musculoskeletal disorders and poorer mental health during retirement, and the number of concussions in players’ careers.