Nick Medina
WRIT 340
Townsend
Illumin Article
Should You Let Your Kids Play Football?
Understanding the Link Between Football & Chronic Traumatic Encephalopathy
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Abstract
Alarming new evidence backed by specialists such as Dr. Bennet Omalu has shown that athletes who experience repeated head trauma could develop a serious type of brain damage called chronic traumatic encephalopathy (CTE). Chronic traumatic encephalopathy is a progressive neurodegenerate brain disease found in people with a history of repetitive brain trauma. It has been found in athletes across multiple sports like boxing, football, and wrestling. 17% of individuals who have repetitive concussions or mild traumatic brain injuries develop CTE. It is caused by the build-up of the malfunctioning tau protein throughout the brain. If CTE progresses long enough, the patient’s brain exhibits actual physical atrophy, much like the brains of front temporal dementia or Alzheimer’s patients.
Dr. Omalu first discovered CTE in 2002 examining the brain of former Pittsburgh Steelers lineman Mike Webster. He began obtaining brains of deceased NFL players, finding tau protein deposits in all of his subjects. One of his subjects, Chris Henry, never sustained a concussion, revealing that the threshold of the amount of head trauma causing CTE is lower than previously thought. CTE has even been found in deceased college and high school football players. But there is hope as a UCLA study this year was able to identify tau protein deposits in 5 former NFL players. Research has also shown that the key for treatment lies tau protein inhibition.
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Introduction
Football is the most popular sport in America. The Super Bowl is one of the most popular worldwide events in the world. Every young man wants to play football for his high school team. Professional athletes, particularly football players, are glorified and serve as role models for the youth of this country. But as a responsible parent, would you let your child play football if you knew the risks of the game on players’ brains? Concussions are a part of the game of football and happen all the time at all ages simply because football is a physical sport. In fact there are 67,000 diagnosed concussions in high school football every year, with at least one player sustaining a mild concussion every game [1]. But, alarming new evidence backed by specialists such as Dr. Bennet Omalu has shown that athletes who experience repeated head trauma could develop a serious type of brain damage called chronic traumatic encephalopathy (CTE). CTE is dangerous because it inhibits the normal functions of the brain, which can result in Parkinson’s or dementia.
The Disease
Chronic traumatic encephalopathy is a progressive neurodegenerate brain disease found in people with a history of repetitive brain trauma. It has been found in athletes across multiple sports like boxing, football, and wrestling. 17% of individuals who have repetitive concussions or mild traumatic brain injuries develop CTE [2]. It is caused by the build-up of the malfunctioning tau protein throughout the brain, which is abnormal to the human brain. Tau is primarily a neuronal protein that is naturally found in the brain, where it binds to and stabilizes the microtubule assembly of neurons. The tau protein plays a central role in cognition. Brain trauma initiates a molecular event leading to
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hyperphosphorylation of tau, resulting in its malfunction and microtubule destabilization
[3]. Figure 1 demonstrates the affects of malfunctioning tau protein. Destabilized microtubules become incapable of neurite growth and fast axonal transport, and neurodegeneration is the outcome. Once initiated, neurodegeneration does not simply stop at the point of the original injury, but rather the malfunctioning tau spreads like a virus across the frontal and temporal area of the brain [3]. If CTE progresses long enough, the patient’s brain exhibits actual physical atrophy, much like the brains of front temporal dementia or Alzheimer’s patients.
Figure 1: Comparison of Neurons with Functional & Non-Functional Tau Proteins
Source: [3]
Brain trauma was found to result in a 3.3-fold increase in the future risk of nonfunctional tau [3]. The nonfunctional tau protein impairs the normal functions of the brain in its early stages and then eventually kills brain cells in the latter stages of the
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disease. The protein is present in the brain when the brain is hit, but disappears when the brain cells kill it. But after multiple blows to the head, the brain cells cannot keep up with the protein and die. Thus it is the repetition of brain trauma that initiates the neurodegeneration caused by malfunctioning tau proteins.
The symptoms of CTE are gradual and progress rapidly with time. These symptoms can be described in three stages. The first stage is disordered cognition, most pronounced in the areas of attention, concentration, memory, orientation, etc. This stage is hard to detect, especially as many people mistake these symptoms as other minor medical problems. It is probable that many retired NFL players have stage 1 CTE. The second stage involves progressed first stage symptoms: social instability, memory loss, erratic behavior, and initial stages of Parkinson disease. The third and final stage of CTE is full-blown
Parkinson’s or dementia [2]. The following brain and microscopic sections demonstrate visuals of the 3 stages of CTE and the increasing tau protein deposition.
Figure 2: Progression of the 3 Stages of CTE
Source: [4]
The Man Who Found the Problem
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CTE is an old disease because it is either undiagnosed or attributed to similar diseases such as dementia or Parkinson’s. Upon discovery, CTE could only be identified posthumously by an examiner specifically looking for the microscopic tau protein deposits.
The face of CTE research is Dr. Bennet Omalu who is a forensic neuropathologist at the
West Virginia University Brain Injury Research Institute, which means he examines deceased people’s brains. Dr. Omalu examined the brain of former Pittsburgh Steelers lineman Mike Webster in a routine autopsy in 2002 [5]. What he saw in the brain was that of an elderly patient with Alzheimer’s disease, not that of a 40 or 50 year old. This is what he saw:
Figure 3: Comparison of Mike Webster’s Brain Section vs. Patient Without CTE
Source: [2]
He was the first to assert that former NFL players had been suffering from dementia pugilistica, a condition identified in a boxer’s brain in 1928 [2]. This was the first CTE diagnosis since then, disproving the prevailing notion that this condition was restricted to boxers. He began obtaining brains of former NFL players who died suspiciously such as
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suicide or tragic deaths as opposed to natural causes. He found the same damaged brains with tau protein deposits in all of his subjects.
CTE in the NFL
All of the deceased NFL players that Dr. Omalu has examined with CTE suffered and had behavioral problems such as depression, drug abuse, suicide, and erratic behavior.
Among the first of his CTE discoveries were Terry Long and Andre Water who both committed suicide as a result of depression. In 2007, the fourth player to be diagnosed with
CTE was offensive lineman Justin Strzelczyk who died at the age of 36 in a car crash going against the flow of traffic. He had bipolar disorder, was on anti-depressants, and already had purchased a family headstone [6]. More recently in 2011, former Pro Bowl safety Dave
Duerson shot himself in the chest leaving a suicide note specifically stating that he wanted his brain to be used for research [7]. These former players resulted in suicide because of the suffering caused by neurodegeneration The tragic part about CTE is that there are probably many more former NFL players that are experiencing similar symptoms.
Most of the early studies of CTE have been in NFL players who have endured long careers and sustained multiple concussions. But what if you are 26 and have never had a concussion? Such is the tragedy of Chris Henry. Henry was an active NFL wide receiver who had a lot of off the field problems with the legal system such as assault, substance abuse, and gun charges. In the middle of the 2009 football season, Henry fell out of a moving truck driven by his fiancé after a domestic dispute and died. Not surprisingly, Dr. Omalu examined his brain and found traces of CTE [8]. What makes Henry’s case different than all the others was that he was so young and had never sustained concussions. This is very significant in CTE research because it was the first time an active NFL had been diagnosed
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with the disease. But more importantly, it could mean the threshold of the amount of head trauma causing it is lower than previously thought.
Chris Henry reveals to us that you don’t have to sustain a concussion to develop
CTE, but rather just multiple blows to the head. Before Chris Henry’s case, parents may have dismissed CTE as an issue that only a tenured professional football player has to deal with. But now, Henry’s case has brought CTE to all of our homes because high school football players can legitimately be at risk.
CTE in Youth
As Dr. Omalu and other specialists have become more aware of the disease, they have discovered it in lower and lower levels of organized football, showing the true risk of the disease. In 2010, a University of Pennsylvania offensive lineman named Owen Thomas committed suicide at the age of 21 and was later identified to have CTE [9]. Thomas never missed a game due to a concussion but was known as a hard hitter. Later that year, 17-year old Nathan Stiles died after his high school homecoming football game because of second impact syndrome, that is receiving a second concussion before symptoms from the first one have subsided [10]. Nathan Stiles demonstrated traces of CTE while only having sustained two concussions in his career.
New Research & Treatments
What is most scary about CTE is that it cannot be detected until an autopsy and the damage is thought to be irreversible. But as time passes, new data helps alleviate the unknown element of the condition. In January 2013, a UCLA study revealed the results of positron emission tomography scans of five undisclosed NFL players showed images of the
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tau protein buildup, which is the first time it has been identified in living people. This was done by injecting the patients with a chemical marker known as FDDNP, which binds to the neurofibrillary tau tangles. The procedure allows the tau protein to be identified in scans and is the same procedure that Alzheimer’s patients undergo. Each of the five players had sustained at least one concussion in their career [11]. The following scans demonstrate some of the findings in the study, comparing brain scans of football players with CTE with a normal brain. The red and yellow concentrations are the tau protein deposits highlighted by FDDNP.
Figure 4: Scans of UCLA Study Identifying Tau Protein Deposit in Living NFL Players
Source: [11]
Identifying tau protein buildup in living people is a big step in the treatment in CTE and could influence an individual’s decision to continue to play after sustaining a concussion or multiple hard hits. This isn’t definitive and may only be the case for people with serious head trauma, but at least it could help to determine a threshold of when players should call it quits. It could also lead to a form of preventative treatment of CTE in football players.
Another possible route for treatment is to model procedures that Alzheimer’s patients undergo. Alzheimer’s is fundamentally similar to CTE in that deposits of
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neurofibrillary tangles composed of hyperphosphorylated tau protein cause it. In fact, researchers have recently been targeting the tau protein in hopes to prevent Alzheimer progression. There are various therapeutic strategies to counter tau hyperphosphorylation:
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Microtubule-Stabilizing Agents: use of neuroprotective peptides to prevent tau protein from malfunctioning, though doesn’t prevent tau aggregation [12]
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Hsp90 Inhibitors: Hsp90 binds to hyperphosphorylated tau preventing its degradation by the proteasome [12]
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Extracellular Tau Oligomers: functional tau protein cultured in vitro and introduced in the hippocampi to account for loss of functional tau protein [12]
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Macroautophagy: tau protein aggregates can be degraded within membrane bound structures called autophagosomes, such as the immunosuppressant drug rapamycin
[12]
The only issue with these therapeutic strategies is that they are still experimental and antitau medications but they aren’t on the market. But CTE patients still could undergo the routine Alzheimer treatment procedures in hope to prevent or delay progression.
Conclusion
Despite recent breakthroughs of CTE, the research is limited and there are still many unknown elements of the disease. The bottom line is that anyone who is exposed to repeated blows to the head is at risk to develop CTE. This maybe a serious issue for our children as well. We need to understand the risks of playing contact heavy sports such as football, hockey, and even wrestling. But there is hope as the tau protein is the key to treating CTE, and even other diseases such as Alzheimer’s.
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Works Cited
[1] Broglio SP, Sosnoff JJ, Shin S, He X, Alcaraz C and Zimmerman J. Head Impacts during high school football: a biomechanical assessment. J. Athl Train. 2009;44:342-349.
[2] McKee, Ann C. “Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy following Repetitive Head Injury.” J. Neuropathol. Exp. Neurol. National Institute of Health.
July 2009. 709–35. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945234/.
[3] Zakowicz, Halina. “What Does Tau Protein Have to do with Football, Dementia, and
Suicide?” Promega. March 21, 2011. http://promega.wordpress.com/2011/03/21/whatdoes-tau-protein-have-to-do-with-football-dementia-and-suicide/.
[4] Staff. "What is CTE?" Center for the Study of Traumatic Encephalopathy. http://www.bu.edu/cste/about/what-is-cte/.
[5] Howard, Johnette. “Chris Henry data sound football alarm.” ESPN. June 29, 2010. http://sports.espn.go.com/espn/commentary/news/story?page=hoiward/100629.
[6] Schwarz, Alan. “Lineman, Dead at 36, Exposes Brain Injuries.” The New York Times. June
15, 2007. http://www.nytimes.com/2007/06/15/sports/football/15brain.html.
[7] Lopresti, Mike. “Is Junior Seau Death Part of a Bigger Problem?” USA Today. May 3,
2012. http://usatoday30.usatoday.com/sports/columnist/lopresti/story/2012-05-
02/lopresti-junior-seau-dave-duerson/54709254/1.
[8] Schwarz, Alan. “Former Bengal Henry Found to Have Had Brain Damage.” The New York
Times. June 28, 2010. http://www.nytimes.com/2010/06/29/sports/football/29henry.html?src=mv&_r=0.
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[9] Meyer, Michelle. “Are You Ready for Some . . . Research? Uncertain Diagnoses, Research
Data Privacy, & Preference Heterogeneity.” Harvard Law Bill of Health. February 3, 2013. https://blogs.law.harvard.edu/billofhealth/2013/02/03/are-you-ready-for-someresearch-uncertain-diagnoses-research-data-privacy-preference-heterogeneity/.
[10] Kounang, Nadia. “Brain Bank examines athletes’ hard hits.” CNN. January 27, 2012. http://www.cnn.com/2012/01/27/health/big-hits-broken-dreams-brainbank/index.html.
[11] Fainaru, Steve. “CTE found in living ex-NFL players.” ESPN. January 22, 2103. http://espn.go.com/espn/otl/story/_/id/8867972/ucla-study-finds-signs-cte-livingformer-nfl-players-first-time.
[12] Davidowitz, Dr. Eliot J. “Targeting tau for Alzheimer’s disease and related neurodegenerative disorders.” Drug Discovery World. Fall 2012. http://www.ddwonline.com/therapeutics/p191020-targeting-tau-for-alzheimer’s-disease-and-relatedneurodegenerative-disorders-fall-2012.html
Biography
Nicholas Medina is a junior at the University of Southern California majoring in Industrial &
Systems Engineering. He is also a member of Zeta Beta Tau Fraternity and plays shortstop for the USC Club Baseball team.
Contact Info: 650-580-8279
Multimedia Suggestions nrmedina@usc.edu
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Animation of football player sustaining a blow to the head. The camera then zooms into to the brain at the microscopic level showing the malfunctioning tau protein deposits appearing.
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Animation of the normal neuron turning into a diseased neuron after hyperphosphorylation of tau protein.
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