Chronic Traumatic Encephalopathy: The Aftermath of Playing America's Favorite Sport

Millions of children share the dream of becoming a professional football player in the National Football League (NFL), but it is a dream that very few achieve. Some will earn the chance to play in high school, a smaller percentage will be able to play at the collegiate level, and only the best will be chosen to play in the NFL. The athletes who beat the odds and make it to the NFL do not make it by accident. 

To play in the NFL requires endless years of hard work, dedication, and sacrifice. Players give up time with friends and family, holidays, and endure grueling training schedules all to play in the league. The boisterous noise from the crowd, the rush of adrenaline on game day, and the financial stability that comes with being a professional athlete in the NFL is enticing. But, what if the very thing you have been striving for since you were a kid puts you and your future at risk? What if the toll that the beloved game puts on your body is irreversible, leaving you to suffer the detriments of the violent sport long after you exit the field for the final time? This was unfortunately a reality for many former football players who suffered from Chronic Traumatic Encephalopathy (CTE). Chronic traumatic encephalopathy (CTE) is a progressive and fatal brain disease associated with repeated traumatic brain injuries (TBIs), including concussions and repeated blows to the head [1]. The types of injuries that lead to CTE are common in American Football [2]. This article will explain the neurological underpinnings of CTE, its psychological and behavioral effects, and how future bioengineering may help identify CTE antemortem.

Although brain injuries have a history as long as human existence, CTE was first described in 2002 by Dr. Bennet Omalu. He was performing an autopsy on the late Mike Webster, a former NFL center, and discovered evidence of a neurological disease similar to Alzheimer’s Disease. Omalu knew the condition was distinct from Alzheimer’s based on Webster’s age, symptoms before death, and neurological changes [3]. Tau proteins, a cytoskeletal protein that primarily stabilizes microtubules in the axons of neurons, were observed in abnormal clusters-called neurofibrillary tangles-in Webster’s brain. Unlike neurofibrillary tau-tangles present in Alzheimer’s disease, those associated with CTE lack corresponding amyloid-beta plaques [4], can be perivascular, and are commonly found in superficial cortical layers [5]. The distinctive pattern of these neurofibrillary tangles had never been seen before, leading Dr. Omalu to pronounce the newfounded disease as Chronic Traumatic Encephalopathy. 

CTE is a neurodegenerative disease that has been associated with repeated traumas to the head. Individuals such as Frank Gifford, Ken Stabler, Junior Seau, Aaron Hernandez, and Demaryius Thomas were diagnosed with CTE postmortem based on the shared neuropathological characteristics of the degenerative disease [6]. There was a common denominator among these five individuals: they played professional football. Football is one of the most physically violent sports, and the prevalence of blows to the head in football is higher than the majority of all sports [7]. In fact, athletes who participate in tackle football for more than 14.5 years are ten times more likely to develop CTE than those who participate for less than 4.5 years [8]. The toll of repetitive blows to the head over a long playing career is detrimental to the brain. 

The brain is not a static organ in the head. Instead, it is suspended in a viscous cerebrospinal fluid which cushions movement when force is applied. However, when an individual is subjected to particularly violent forces, the likes of which are common in football and high impact sports, the CSF cushion is insufficient, and the brain can slam into the walls of the skull [9]. The rapid acceleration and deceleration that comes with these brain movements can cause neurons to rotate, stretch, and tear. A violent blow to the head could result in a concussion or a Traumatic Brain Injury (TBI) due to large amounts of rotational and translational force on the brain. The toll of many microscopic brain injuries can lead to the abnormal accumulation of hyperphosphorylated tau protein [10]. 

Repetitive blows to the head can cause an influx of calcium into neurons, activating enzymes called kinases, a catalyst that transfers a phosphate group from energy molecules (ATP) to specific molecules like tau [11]. Tau proteins become hyperphosphorylated when excessive sites on the protein become fully saturated due to the binding of a phosphate group [12]. Increased levels of hyperphosphorylated p-tau202 , p-tau231, p-tau396  have been uniquely found in CTE [1]. When tau becomes hyperphosphorylated, the protein becomes insoluble which ultimately can cause axonal and neuronal impairment.  

The normal physiological function of tau is to stabilize microtubules, a structural component of neurons. Microtubules are the internal skeleton of neurons that stabilize neuronal components like dendrites and axons that receive and transport information from one neuron to the next. Hyperphosphorylated tau proteins misfold, detach from microtubules, and form insoluble neurofibrillary tangles [13]. Hyperphosphorylated tau is cytotoxic to neurons, leaving microtubules without a stabilizing protein. Subsequently, microtubules become free to break down, leaving axons without a cytoskeletal structure. When microtubules break down due to the dissociation of hyperphosphorylated tau proteins, it can cause neuronal impairment and death [14]. The majority of brain cells do not divide and replicate, unlike other bodily cells, so they can not renew themselves [15]. Because of this, CTE causes irreversible damage, leading to possible psychological changes in the brain.   

The anatomical changes and symptoms seen in individuals suffering from CTE can take months, years, or even decades to start developing [16]. Symptoms of CTE can be undetectable at its earliest stages, but as the disease progresses, the symptoms can become apparent and severe. Symptoms of CTE include, but are not limited to, impaired judgment, mood swings, anxiety, memory loss, difficulty thinking, impulsive behavior, aggression, parkinsonism, depression, and suicidality [15]. Symptoms of CTE vary depending on which regions of the brain are affected as well as the severity of the progression of the disease.

The amygdala is a region of the brain, found in the medial temporal lobe, that is responsible for emotional regulation, memory encoding, and survival instincts [17]. If neuronal impairment or death occurs in the amygdala, it may influence an individual’s mood and behavior, making symptoms like memory loss, anxiety, and depression increasingly likely to arise. 

The frontal cortex is another region of the brain susceptible to damage caused by CTE. This region is primarily responsible for cognition motor control, impulse control, decision-making, and judgment. The progression of CTE in the frontal cortex may lead to poor decision-making, impulsivity, lack of concentration, trouble retrieving memories and a loss of sense of social appropriateness [18].

 CTE tends to start focally, but slowly spreads to other regions of the brain. In stage I CTE, p-tau pathology is most commonly found in the lateral or superior frontal cortices, but as the disease may progress to stage IV (the most severe stage), most of the cerebral cortex and medial temporal lobe is affected by ubiquitous p-tau pathology [2] . The autonomic, motor function, and cognitive impairment an individual with stage IV CTE may experience is overwhelming and detrimental to their quality of life. 

As of 2023, the only way to diagnose CTE is post-mortem through an autopsy. However, there have been recent breakthroughs in research that may allow neurologists to determine if an individual has CTE while they are living. Positron Emissions Tomography (PET) is a type of imaging scan that uses radiotracers to visualize metabolic and physiological processes in the body [19]. Radiotracers are injected into the bloodstream and bind to specific molecules. Once the radiotracers decay, positrons are emitted, which ultimately causes gamma rays to be produced and detected by the PET scanner, creating a 3-D map of metabolic processes in the body [19]. 

The purpose of using a PET scan for someone who may have CTE would be to observe if the radiotracers, specific to the unique tau proteins linked with CTE, bind to the protein or not [20]. If the radiotracers do bind to this type of tau, it would provide strong evidence that the individual is positive for CTE. The radiotracers designed to test for CTE are still in development and are being engineered to bind to CTE-specific tau proteins. Alzheimer’s is a neurodegenerative disease similar to CTE that can be diagnosed through a PET scan, making researchers confident that they can design radiotracers using some of the framework from radiotracers used for Alzheimer’s [20]. The pattern of abnormal tau proteins are distinct for both diseases, so the same radiotracers can’t be used for CTE, but the similarity between the two tauopathies makes it optimistic that similar radiotracers can be designed for CTE, creating the possibility for individuals to be diagnosed with CTE and treated with appropriate medications antemortem.  

Chronic Traumatic Encephalopathy is a disease that the world is still trying to fully understand. The complexity of the brain and neurological diseases makes CTE intricate. The anatomical changes are severe, progressive, and irreversible, leaving individuals to suffer in their own bodies for the rest of their lives. Researchers have shown evidence that repetitive, subconcussive or concussive blows to the head are associated with CTE. Football is an aggressive sport with players accelerating at each at high speeds. Contact to the head is abundant due to the nature of the sport, which is likely associated with the fact that over 91% of 376 former NFL players have been diagnosed with CTE posthumously [21]. Although there is currently no cure nor a way to diagnose the disease in those living, CTE is preventable. Increasing the age limit for tackle football, limiting contact in practice, equipping state-of-the-art headgear protection, or abstaining from tackle football participation are prevention methods that should be considered to prioritize the health of football athletes. Abolishing America’s favorite sport isn’t entirely necessary, but athletes must be fully aware of the risks that may come with playing it, the same way cigarette packs in the U.S. are mandated to alert consumers of the serious health risks that may come with smoking. CTE researchers have presented their evidence, it’s now up to athletes, parents, football leagues, and policy makers to decide the future of player health in football.

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