Eenie, Meenie, Miney, Tau

Mike Webster, a celebrated Hall of Fame center for the Pittsburg Steelers, played in 245 NFL games, including his time with the Kansas City Chiefs, and was hit in the head thousands of times. “Iron Mike” died 24 September 2002 at the age of 50. Dr. Bennet Omalu, a neuropathologist, was assigned to perform the autopsy on the body and the brain. Omalu made a groundbreaking discovery, seeing something in Webster’s brain that had never been found in a football player’s brain before and should never have been present in the brain of a 50-year-old man (Breslow, 2013; Concussion Legacy Foundation [CLF], 2017).

 

 

If you’ve read at all about concussions you’ve probably come across the term Chronic Traumatic Encephalopathy (CTE). CTE is a progressive degenerative disease of the brain found in athletes, military veterans, and others with a history of repetitive brain trauma. The repetitive brain trauma causes a buildup of a protein called tau.  The aggregation of tau is toxic, slowly killing cells of the brain, as also seen in Alzheimer’s disease (CLF, 2017; Lerner, 2016; Mandelkow & Mandelkow, 2012).

cta.jpg

The tau protein in itself is not inherently dangerous. Tau is a protein in the brain which helps stabilize brain cell structure and internal transport system (CLF, 2017; Lerner, 2016). Tau links microtubules that run through axons of the brain, two tau proteins in each link; the heads of the tau proteins are each bound to a microtubule, and the tau tails meet in the middle and are bound together, but this bound isn’t permanent (Lerner, 2016). Because of its hydrophilic nature tau does not adopt the typical compact, folded structure of most proteins. Instead, it is “natively unfolded” and “intrinsically disordered”, meaning its highly flexible and mobile, kind of like pipe cleaners you use in arts and crafts  (Mandelkow & Mandelkow, 2012). Motion within the brain easily detaches the tail ends of the tau protein and causes them to reattach to a new tau protein tail. This binding and unbinding allow for easy sliding between microtubules without damage (Lerner, 2016).

repetitive trauma

However, repeated injury to the brain causes neurons to stretch and tear.  Rapid jolts in concussive episodes do not allow the bound portions of tau tails to untangle and bond with a new tau partner. High-velocity forces of a concussion do not allow to tail ends of the tau proteins to unbind and the forces are exerted on the microtubules instead, causing damage (Lerner, 2016). The tau protein then changes its shape, clumps together with another tau, and spreads while slowly killing neurons. In CTE, clumps of tau tend to first appear around blood vessels within the brain sulci (valleys between brain cortical folds), and then spreads to other areas of the brain (CLF, 2017).

high velocity.gif

 

axons under stress

The danger of chronic brain injury is the guaranteed risk for memory loss, confusion, impaired judgment, paranoia, impulse control problems, aggression, depression, and eventually progressive dementia (CLF, 2017).

A study by Shahim et al. (2014) looked at blood biomarkers after a concussion in professional ice hockey players and found that the highest concentrations of total tau were measured immediately after injury, tau levels declined after the first 12 hours, and a second peak of tau levels occurred between 12-36 hours post-injury. Most importantly, tau levels 1 hour post-concussion concussion predicted the number of days it took for the concussion symptoms to resolve and the players to have safe return to play. This suggests that total tau levels may potentially be a way to monitor recovery in patients with brain injury (Shahim et al., 2014)Since diagnostic imaging is not able to help health care professionals predict concussion outcomes and recovery, perhaps these findings with help pave the way for more efficient, more informed, and

Since diagnostic imaging is not able to help health care professionals predict concussion outcomes and recovery, perhaps these findings with help pave the way for more efficient, more informed, and better-monitored recovery and return to play.

head but.gif

 

Author: Alyssa Reidy, LAT, ATC, CCTP

References

Breslow, J. (2013). The Autopsy That Changed Football. [online] FRONTLINE. Available at: http://www.pbs.org/wgbh/frontline/article/the-autopsy-that-changed-football/

Concussion Legacy Foundation [CLF] (2017). What is CTE?. [online] Concussion Legacy Foundation. Available at: https://concussionfoundation.org/learning-center/what-is-cte

Lerner, E. (2016). Penn study determines breakaway protein is critical in concussions. [online] Penncurrent.upenn.edu. Available at: https://penncurrent.upenn.edu/2016-01-14/latest-news/penn-study-determines-breakaway-protein-critical-concussions

Mandelkow, E. and Mandelkow, E. (2012). Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration. Cold Spring Harbor Perspectives in Medicine, 2(7), p.a006247

Shahim, P., Tegner, Y., Wilson, D., Randall, J., Skillbäck, T., Pazooki, D., Kallberg, B., Blennow, K. and Zetterberg, H. (2014). Blood Biomarkers for Brain Injury in Concussed Professional Ice Hockey Players. JAMA Neurology, 71(6), p.684

 

 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s