Researchers Uncover Potential Link Between CTE and ALS

Mathew Shanley

With Super Bowl Sunday just two days away, it’s easy for fans to start getting excited about the prospect of basing an entire day around a football game.

This year, more than ever, though, it’s difficult for anyone to think about the sport without associating it with the dark cloud hovering above the sport, and its elephant in the locker room – chronic traumatic encephalopathy (CTE).

To make a serious subject even more serious, new research suggests that there could be a possible connection between CTE and amyotrophic lateral sclerosis (ALS). National Football League (NFL) veterans Steve Gleason, Dwight Clark, and others were diagnosed with ALS after their playing careers ended, and CTE has also been found in military veterans, who are twice as likely as non-veterans to be diagnosed with ALS.

Approximately 5% of CTE cases result in patients demonstrating the clinical or pathological characteristics of ALS, however, whether the 2 conditions are related has remained a mystery. Michael Strong, M.D., and a team of researchers from the Schulich School of Medicine and Dentistry at Western University in Canada compared molecular and pathological signatures of post mortem brain and spinal cord tissue obtained from people who lived with CTE and CTE with ALS (CTE-ALS) compared to controls.

CTE, a progressive degenerative neurological condition, most commonly presents in those with a history of repetitive brain trauma, including symptomatic concussions and asymptomatic contact to the head. Diagnosis can only be made via autopsy; however, clinical presentation often begins with a lack of behavioral control, including impulsive actions or violence, triggered by rage, paranoia, anxiety, or depression.

ALS, also a progressive neurodegenerative disease, affects the nerve cells in the brain and spinal cord, as motor neurons reach from the former to the latter to the muscles throughout the body. Early symptoms include muscle weakness or stiffness, and research suggests that professional football players are four times as susceptible to develop the disease than those in the general population.

While the two diseases present differently, confusion between them is not uncommon because both are characterized by cognitive impairment.

Strong’s study focused on tau, a protein that forms clumps (aggregates) in the brain, resulting in eventual cell death. Phosphorylation, a specific pathological modification of tau, sets off a molecular cascade involving the activation of kinase, causing cell death in the brain. The researchers found a commonality of the phosphorylation of tau in aggregates of those with CTE and CTE-ALS in the brain and spinal cord, uncovering a new acuity into the disease pathway.

A model rat with moderate traumatic brain injury was also used to exhibit similar pathology, replicating the features observed in post mortem tissue and further supporting the connection between the two conditions.

Due to the high complexity of both diseases, more long-term studies are necessary for a full understanding of the connection. The recent analysis warrants a larger study of more people with CTE and CTE-ALS to confirm results, but continued studies could potentially uncover viable CTE-ALS biomarkers and therapeutic options.

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  1. Moszczynski AJ, Strong W, Xu W, McKee A, Brown A, Strong MJ. Pathologic Thr175 tau phosphorylation in CTE and CTE with ALS. Neurology, 2018; DOI: 10.1212/WLN.0000000000004899.
  2. Researchers Uncover a Common Link Between ALS and CTE. Washington D.C.: The ALS Association; January 18, 2018. Accessed February 1, 2018.
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