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CTE Study

CTE Linked to Somatic Genetic Mutations, New Study Finds

Researchers use single-cell genome sequencing to show DNA damage similar to Alzheimer’s disease in the brains of patients with CTE.

Chronic traumatic encephalopathy (CTE) – most often found in athletes playing contact sports – is known to share similarities with Alzheimer’s disease (AD), namely the buildup of a protein called tau in the brain. New research published today in Science finds even more commonalities between the two at the genetic level, showing CTE (like AD) is linked to damage to the genome.

The research team, a collaboration between Boston Children’s Hospital, Mass General Brigham, and Boston University, used single-cell genomic sequencing to identify somatic genetic mutations (changes in DNA that occurs after conception and are not hereditary).  They analyzed hundreds of neurons from the prefrontal cortex of 15 individuals with CTE and 4 individuals with RHI but without CTE and compared their findings with 19 neurotypical controls and 7 individuals with AD.

The team found neurons from individuals with CTE had specific abnormal patterns of somatic genome damage that closely resemble those seen in AD. Notably, individuals who had RHI without CTE didn’t have these changes. They also observed that the brains of individuals with CTE showed signs of damage equivalent to 100+ years of excess aging.

“Our results suggest that CTE develops through some process in addition to head trauma,” said Chris Walsh, MD, PhD, Chief of the Division of Genetics and Genomics and Investigator of the Howard Hughes Medical Institute at Boston Children’s and co-corresponding author of the study. “We suspect it involves immune activation in a way similar to Alzheimer’s disease, that may happen years after the trauma.”

RHI most often occurs during contact sports such as American football, hockey, or rugby or during military service. CTE has been found in the brains of teenagers and young adults playing only amateur sports, as well as in older athletes. Recent research from co-corresponding author Ann McKee, MD, William Fairfield Warren Distinguished Professor of Neurology and Pathology at Boston University and director of BU’s CTE Center found RHI causes brain damage in young people even before CTE. Their study, published last month in Nature, suggested that RHI-related brain injury occurs before the onset of tau deposition as CTE. This new research published today adds to this growing evidence base.

“One of the most significant aspects of our work is the introduction of a new, single-cell genome approach to CTE,” said co-corresponding author Michael Miller, MD, PhD, a neuropathologist and principal investigator in the Mass General Brigham Department of Pathology. “Our study provides further evidence that CTE is a bona fide neurodegenerative disease defined by its unique neuropathological features.”

Given the shared mechanisms found between CTE and AD, there could be promise in identifying shared novel targets for these two neurodegenerative diseases.