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There has been an increase in the last five years of the public recognition of one of the conditions affecting football players across the country who have had multiple concussions.  There has even been discovery that the football industry knew these men were facing a lifetime of effects but did not tell the public.  Due to those developments and efforts toward educating the public, society has become more aware of the other activities that are also leading to repetitive concussions; such as, soccer, basketball, wrestling and baseball; as well as from repetitive brain trauma such as that experienced by soldiers returning from Iraq and Afghanistan

Previously, the belief had been that, after a head injury, most commonly called a concussion, a person needed a very short period of time to be cleared, and without lasting symptoms, could return to play.  However, it is now known that the brain does not heal as quickly as was first thought, and that there needed to be a series of cognitive tests with time between each to ensure that athletes were truly ready to return to the field.

Unfortunately for athletes who have been playing longer or whose careers are behind them, the effect of returning to play too soon or of having multiple instances of brain trauma has resulted in many being diagnosed after death with CTE or chronic traumatic encephalopathy.  CTE is a neurodegenerative disease that is characterized by changes in thinking, mood or behavior that progresses overtime and in severe cases always leads to dementia.

What is known about CTE is increasing as athletes and soldiers have succumbed to this horrible disease.  The other issue for identifying CTE is that, according to the National Institute of Health (NIH), it currently can only be definitely detected after death by autopsy.  However, there is hope for detecting it sooner according to the very recent findings using PET scans with a tau radiotracer.

Is it in the Genes? 

At this point, there is no known genetic factor that causes some individuals who have had repetitive brain injury to develop CTE while others do not.  There has been recent speculation, due to a very small 2018 study of only 86 Caucasian American football players, on whom autopsies were conducted, that there may be a gene that could be protecting some players from developing the same degree of CTE or dementia.  However, many red flags arise when trying to take that information to determine who will not be affected by these diseases even after having years of concussive blows.

The biggest issue with a study like this is that there was no group to use as a control group.  In addition, the autopsies were limited to players whose surviving family agreed to have studied.  As such, the results were more likely to be from families who had seen traits that worried them and that knew to ask for an autopsy.  Beyond those concerns, however, is that the variation in the TMEM106B gene in question, rs3173615(G), which is relatively common even though it is a minor allele, is only correlated to a “somewhat less neuroinflammation and an increase synaptic protein density.”  In lay terms, it found that there was a little less swelling in the tissue in the central nervous system and less ability for brain signals to be received, and that this difference was only noted in players whose autopsies were positive for CTE.  So, there was no decreased likelihood of developing CTE even if the variation was present, just that the symptoms were less severe.

Newer studies are also looking at the possible role of a genetic predisposition based on the apolipoprotein E (APO E) gene, which comes in several variations, one of which is the APOE4 allele.  Among Alzheimer’s sufferers, 40% have this variation on autopsy, but the link is also questionable because the autopsies of these brains demonstrated greater amyloid beta plaques than found in any of the CTE autopsies.

The Future

The best hope is offered in the work being conducted jointly by Harvard Medical School and Boston University.  The two institutions are examining both APOE4 and an aggregate tau risk gene score detected by PET to determine if individuals have predisposing factors. The important distinction between this latest work and the prior two studies discussed above is that the tau factors are derived from studies based on thousands of healthy aging individuals.  This work marks the closest the scientific and medical community has come to understanding the possible genetic markers for who may recover after rest versus who is at risk for permanent brain damage and ultimately CTE.

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