Exploration of serum Lipid-based biomarkers and cognitive behaviours linked to repetitive concussions: The UK Rugby Health study

Abstract
Background
Rugby players in both Union and League face a risk of concussion. Repetitive brain
trauma, particularly without adequate recovery, can lead to post-concussion syndrome
and is associated with an increased risk of neurodegenerative diseases including
Alzheimer’s, ALS, and Parkinson’s.
Method
This study analysed serum biomarkers and cognitive performance in retired male rugby
players with a concussion history (n=34) compared with a non-contact sports group
(n=22). 24-HC, 25-HC, 27-HC, APOE4, triglycerides, and ceramides were measured
using ELISA assays and correlated with each other and previously identified biomarkers
from the UK Rugby Health Study. Cognitive parameters assessed included verbal and
visual memory, processing speed, and executive function. Standardised cognitive
scores were analysed alongside biomarker levels to identify associations between
indicators of brain stress, cognitive performance, and concussion history.
Results
Compared to controls, concussed participants showed reduced 24-HC and increased
25-HC, 27-HC, APOE4, triglycerides, and ceramides. Aβ42 positively correlated with 25-
2
HC (r=0.694, R²=0.482), 27-HC (r=0.651, R²=0.424), and ceramide (r=0.876, R²=0.768).
Tau proteins positively correlated with 25-HC (P-Tau181: r=0.906, R²=0.820; P-Tau231:
r=0.441, R²=0.195) and triglycerides (T-Tau: r=0.826, R²=0.683), and negatively
correlated with 24-HC (P-Tau181: r=0.969, R²=0.8939; P-Tau231: r=0.639, R²=0.409).
Participants with >5 concussions showed deficits in executive function. Raw and verbal
memory positively correlated with 25-HC (Raw: r=0.680, R²=0.462; Verbal: r=0.578,
R²=0.3343), while psychomotor and processing speed negatively correlated with 27-HC
(Psychomotor: r=0.514, R²=0.264; Processing: r=0.529, R²=0.280).
Conclusion
Multiple TBIs without adequate recovery may cause neuronal damage, reflected by
decreased 24-HC and increased 25-HC, 27-HC, APOE4, ceramides, and triglycerides.
These changes correlate with elevated Aβ42 and T-Tau, promoting amyloid plaque and
NFT formation, hallmarks of neurodegenerative diseases such as Alzheimer’s,
Parkinson’s, and ALS. A long-term follow-up is needed to track biomarker progression
and disease development.