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’s 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’s, 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 ± 6.44, and the mean years since retirement from the sport was 7.76 ± 6.69 for participants with a history of substantial concussions (>5 concussions in their career) (n = 30). The mean age was 45.75 ± 11.52, and the mean years since retirement was 6.75 ± 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 (Aβ42, 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 < 0.01; p-tau181: p < 0.05). Although between-group differences in p-tau217, p-tau231, SAA, Nf-L, retinol, and Aβ42 were not significantly different, there was a trend for higher levels of Aβ42, p-tau217, and p-tau231 in the concussed group. Interestingly, the serum-derived exosome sizes were significantly larger (p < 0.01), and serum RBP-4 levels were significantly reduced (p < 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.

Long-term effects of concussions, particularly in contact sport athletes, have been linked to changes in neuronal health. Lipid dysregulation has emerged as a potential contributor to neuronal injury and may serve as a measurable biomarker of brain pathology. This study investigated cognitive scores and serum lipid biomarkers in retired rugby players with a history of concussion to assess their association with concussion exposure. Serum levels of 24-hydroxycholesterol (24-HC), 25-HC, 27-HC, total triglycerides, and ceramide were compared between retired rugby players with a history of repeated concussions (n = 26) and non-contact sport controls (n = 19). ELISA-based quantification and statistical analyses identified significant group differences. Concussed athletes exhibited significantly lower serum 24-HC and significantly higher levels of 27-HC, triglycerides, and ceramide compared to controls, while no significant difference was observed for 25-HC. These findings indicate that repeated concussion is associated with reductions in cognitive performance and persistent alterations in serum lipid profiles. The observed lipid changes, particularly in 24-HC, 27-HC, ceramide, and triglycerides, may serve as measurable biomarkers of concussion-related biochemical alterations, providing a foundation for future studies aimed at monitoring neurological health in at-risk populations.

There is growing interest in understanding the connection between concussions on physical and mental health acutely and, in retirement, on neurodegenerative diseases. In this study, we utilised a “high-impact trauma” (HIT) device to investigate the effects of multiple concussions on the motor activity, and lifespan of the adult female Drosophila melanogaster as well as reactive oxygen and nitrogen species (RONS) levels in the fly brain and body. We found that repetitive hits, while not having acute physical effects, significantly increased long-term mobility deficits, and shortened lifespan, and exacerbated oxidative stress in both the brain and body. Notably, the novel CONKA product (Withania somnifera, Curcuma longa, Melissa officinalis, Rhodiola rosea, Vaccinium myrtillus) demonstrated promising protective effects, including mitigation of motor deficits, extension of lifespan, and reduction of oxidative stress in both the brain and body of the flies. When evaluating the contributions of individual components within the CONKA formulation, Curcuma longa, despite extending lifespan, did not contribute to mobility improvement or oxidative stress amelioration. This suggests that the benefits of CONKA are largely driven by its other four components, which displayed all the positive effects evaluated. The exclusion of Curcuma longa may streamline the formulation without diminishing its brain and body effects following a history of repetitive concussions, although this would require further study to confirm. Oral bioavailability may be an issue with Curcuma longa. Taken together, the findings validate that Drosophila melanogaster is a suitable system to mimic and investigate the effects of repetitive concussions on bodies and brains and assess the effects of health products and drug therapies.

Objectives: This study aims to investigate the long-term effects of multiple concussions on physical function and oxidative stress, as well as the potential protective effects of a novel phytoceutical product (CONKA1) on ageing and brain health of Drosophila melanogaster. Methods: Adult female D. melanogaster flies were exposed to repeated concussive events using a high-impact trauma (HIT) device. The effects of these impacts were assessed on lifespan, motor activity, and levels of reactive oxygen and nitrogen species (RONS) in both the brain and body. The flies were administered a multicomponent supplement (CONKA1), comprising Withania somnifera, Curcuma longa, Melissa officinalis, Rhodiola rosea, and Vaccinium myrtillus, and outcomes were compared to untreated controls. Key findings: CONKA1 improved the lifespan and motor activity and reduced oxidative stress in ageing flies. Repetitive concussion hits significantly increased long-term mobility deficits, shortened lifespan, and exacerbated oxidative stress in both the brain and body, above and beyond normal ageing. CONKA1 demonstrated mitigation of extra motor deficits, reduced lifespan, and exacerbated oxidative stress in both the brain and body of the flies. Conclusions: The findings validate that D. melanogaster is a suitable system to mimic the effects of repetitive concussions and evaluate the effects of novel health products.

Neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) have been associated with long-term effects of concussions, particularly in contact sport athletes. Lipid dysregulation has emerged as a potential contributor to neuronal damage and could serve as an early biomarker of brain pathology. This study aimed to investigate serum lipid biomarkers in retired rugby players with a history of concussion to explore their diagnostic relevance and potential link to neurodegenerative disease risk. A comparative analysis was conducted comparing serum levels of ApoE4, 24-hydroxycholesterol (24-HC), 25-HC, 27-HC, total triglycerides, and ceramide between concussed retired rugby players and non-contact healthy controls. ELISA-based quantification and statistical comparisons were used to identify significant group differences. Retired rugby players exhibited significantly lower serum 24-HC and significantly higher levels of ApoE4, 27-HC, triglycerides, and ceramide compared to controls. No significant difference was found in 25-HC, though some concussed individuals showed elevated levels. These findings align with previous reports in AD, PD, and ALS populations, supporting lipid dysregulation as a hallmark of neurodegenerative progression. Alterations in lipid profiles among concussed athletes suggest potential roles for ApoE4, 24-HC, 27-HC, ceramide, and triglycerides as early biomarkers for concussion-induced neurodegeneration. These findings may guide future diagnostics and post-care strategies for at-risk populations.