CTE, a progressive neurodegenerative disease often linked to contact sports, has long been characterized by tau protein accumulation in the brain, and computer models have suggested that the base of the folds of the cortex experience the greatest strain when a human brain is rotated rapidly. This study is the first to measure patterns of brain degeneration in CTE, and shows that repetitive head impacts are linked to loss of cells, shrinkage, and tau pathology buildup within the folds of the brain. Regional brain atrophy is also prominent in the frontal, hippocampal, hypothalamic, mammillary body, and thalamic areas of the brain.

The study analyzed brain samples from 185 athletes with histories of contact sports and 52 non-athlete controls. Additional key findings include:

• Significant cortical thinning and reduced neuronal density in the brain folds within the frontal cortex, especially in advanced CTE stages.

• A strong association between the duration of contact sports exposure and cortical thinning, indicating a potential cumulative effect of head impacts.

• Evidence that neuronal loss is mediated by tau protein accumulation, while cortical thinning also involves tau-independent mechanisms.

• Synaptic protein changes suggesting a dynamic process of damage and repair in CTE-affected brains.

“The cortical sulcus appears uniquely vulnerable to head impacts, with pronounced neurodegenerative changes occurring in these regions,” said corresponding author Thor Stein, MD, PhD, a neuropathologist at VA and Bedford Healthcare Systems and associate professor of pathology & laboratory medicine at the school. “These findings have significant implications for understanding how CTE progresses and identifying potential biomarkers for early detection.”

This research underscores the need for protective measures in contact sports and offers new insights into the role of neurodegeneration in cognitive and behavioral symptoms of CTE.