The cost of impact

An international team, coordinated by researchers at University Health Network’s Krembil Brain Institute and the University of Toronto’s Tanz Centre for Research in Neurodegenerative Diseases, has found that repeated head impacts have more far-reaching effects than previously thought. 

Repeated head impacts are associated with an increased risk of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease that can cause behavioural issues and cognitive decline. The condition came to prominence after several professional athletes were found, after their deaths, to have had CTE.  

CTE is diagnosed by examining the brain for CTE neuropathological changes after a person dies. These changes are characterized by abnormal accumulations, called aggregates, of a misshapen form of the tau protein in neurons and astrocytes — cells that support neurons — in the brain’s cortex.  

Until now, research has focused almost exclusively on the brain and overlooked another vulnerable part of the nervous system: the spinal cord. 

Senior author Gabor Kovacs, a senior scientist at the Krembil Brain Institute and principal investigator at the Tanz Centre, and his research team set out to address this gap by examining the effects of repeated head impacts on the spinal cord. In this postmortem study, published in JAMA Neurology, the team analyzed brain and spinal cord tissue from 70 people for the presence and severity of CTE-related tau aggregates beyond the brain. 

They found that individuals with CTE neuropathological changes in the brain showed significantly more frequent and severe tau aggregates in their spinal cords than those without CTE, regardless of history of repeated head impacts. Notably, CTE cases also exhibited tau aggregates in spinal astrocytes, which is a feature not seen in other conditions with tau aggregates such as Alzheimer’s disease. 

Among those with CTE, both neuronal and astrocytic tau pathology were more pronounced in people with a history of repeated head impacts, highlighting a cumulative effect of repeated trauma. 

Age further amplified these changes. People over the age of 65 who had CTE and a history of repeated head impacts exhibited the most severe tau aggregates.  

Other protein aggregates in the brain were also seen in the spinal cord, including α-synuclein, amyloid-beta, and TDP-43, which contribute to Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, respectively. These other protein aggregates were also more common in this group, suggesting that repeated head impacts may accelerate age-related neurodegeneration and contribute to the development of other conditions beyond CTE. 

“For too long, the effects of repeated impacts on the central nervous system beyond the brain have been understudied,” says first author and Tanz Centre research fellow Hidetomo Tanaka.  

“It is time we shift the definition of CTE to encompass not only the brain but the spinal cord as well,” says Kovacs, who is also a professor of laboratory medicine and pathobiology at U of T’s Temerty Faculty of Medicine. 

By broadening the scope of CTE research, this work deepens the understanding of trauma-related neurodegeneration and underscores the need for protective strategies to safeguard the spines and brains of those at risk of repeated head impacts. 

Researchers hope these insights may help reduce long-term neurological burden and improve quality of life for people who experience repeated head impacts, including professional athletes long after the end of their sports careers.  

This work was supported by the U.S. National Institutes of Health (NIH), the United States Department of Defense, the Medical Research Council, and UHN Foundation.  

Kovacs has a shared patent for 5G4 synuclein and a patent pending for diagnostic assays for movement disorders. He also reported royalties from Wiley, Cambridge, Taylor and Francis, as well as research support from the Rossy Family Foundation, Edmond Safra Foundation, Krembil Foundation, MSA Coalition, Michael J. Fox Foundation, Parkinson Canada, and the NIH outside of this work.  

This story was originally published by University Health Network.