Neurofilament‐light in former athletes: a potential biomarker of neurodegeneration and progression

Abstract

Background/Objective: This study aimed to evaluate serum neurofilament light chain (NF-L) levels in former professional contact sports athletes with multiple concussions (ExPro) as a potential biomarker of neurodegeneration and predictor of white-matter (WM) abnormality progression. Methods: Concentrations of NF-L in the serum of fifty-two cognitively normal ExPro and twenty-one healthy controls (HC) with no history of concussions were measured using single molecule array (Simoa) technology. Both groups underwent neuroimaging at the time of serum collection. Eighteen of the participants in the ExPro underwent follow-up imaging after 2 years. Results: Levels of serum NF-L were not significantly different between the ExPro and HC. However, in the ExPro group, NF-L levels were positively correlated with the mean diffusivity (MD) of corpus callosum (CC) and fornix, and total ventricular volume. Moreover, NF-L levels in the ExPro group at the first visit were positively correlated with the amount of increase in CC MD at the 2-year follow-up. Conclusions: NF-L levels reflect neuronal changes in the ExPro group and predict the extent of decrease in white matter integrity over time. Serum NF-L might be a biomarker of neurodegeneration and WM abnormality progression in ExPro.

Fluid biomarkers and risk of neurodegenerative disease in retired athletes with multiple concussions: results from the International Concussion and Head Injury Research Foundation Brain health in Retired athletes Study of Ageing and Impact-Related Neurodegenerative Disease (ICHIRF-BRAIN study)

“… 13 This implies that NfL could potentially be used as a marker of ongoing neuroaxonal injury secondary to repeated concussion. 21 In our study, we did not find any difference in plasma NfL concentration between the two study groups. This may suggest that retired athletes with a history of concussions did not have a higher prevalence of neurodegenerative disease, as measured by plasma NfL or that increases in NfL related to acute brain injury may not be persistent in plasma over time.…”

“…13 This implies that NfL could potentially be used as a marker of ongoing neuroaxonal injury secondary to repeated concussion. 21 In our study, we did not find any difference in plasma…”

Effects of docosahexaenoic acid and eicosapentaoic acid supplementation on white matter integrity after repetitive sub-concussive head impacts during American football: Exploratory neuroimaging findings from a pilot RCT

“…The NfL levels observed in the present study are consistent with the range of values observed in previous RSHI studies (<20 pg/ml) ( 96 – 98 ), including the two previous trials examining omega-3 supplementation in this population ( 38 , 39 ), indicating that even the highest values observed at the end of the season are within an expected range. To date, there have been few studies specifically examining the relationship between NfL and neuroimaging-derived white matter integrity in mTBI or RSHI vulnerable populations ( 99 – 102 ). These studies have identified decreased FA and increased mean diffusivity, particularly in the corpus callosum, to be associated with increased NfL ( 99 , 101 , 102 ).…”

Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain

“…Recent advances in immunoassay technologies have enabled reliable detection of NfL in blood and have been utilized in multiple studies to demonstrate high correlation between NfL levels in CSF and blood 5 . An increased concentration of NfL in blood (serum NfL level) or CSF has been reported in numerous studies of neurodegenerative diseases 6 as well as concussion 7,8 . Since collecting blood-based biomarkers is more practical and desirable for extensive clinical trials as compared to CSF-based biomarkers, numerous studies have analyzed serum NfL levels in the context of different neurological disorders such as multiple sclerosis 9,10 , dementia 11 , progressive supranuclear palsy 12 , traumatic brain injury (TBI) 13 , Parkinson's disease 14 , Alzheimer's disease 15 , and Huntington's disease 16 .…”