Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described. In this study, we quantified three key neurodegenerative measures, including cortical thickness, neuronal density, and synaptic proteins, in contact sport athletes (n = 185) and non-athlete controls (n = 52) within the sulcal depth, middle, and gyral crest of the dorsolateral frontal cortex. Cortical thickness and neuronal density were decreased within the sulcus in CTE compared to controls (p’s < 0.05). Measurements of synaptic proteins within the gyral crest showed a reduction of α-synuclein with CTE stage (p = 0.002) and variable changes in PSD-95 density. After adjusting for age, multiple linear regression models demonstrated a strong association between the duration of contact sports play and cortical thinning (p = 0.001) and neuronal loss (p = 0.032) within the sulcus. Additional regression models, adjusted for tau pathology, suggest that within the sulcus, the duration of play was associated with neuronal loss predominantly through tau pathology. In contrast, the association of duration of play with cortical thinning was minimally impacted by tau pathology. Overall, CTE is associated with cortical atrophy and a predominant sulcal neurodegeneration. Furthermore, the duration of contact sports play is associated with measures of neurodegeneration that are more severe in the cortical sulcus and may occur through tau-dependent and independent mechanisms.

神经退行性变是许多神经系统疾病的开创性特征。慢性创伤性脑病 （CTE） 是由重复头部撞击 （RHI） 引起的，其特征是脑沟 tau 病变。然而，尚未描述 CTE 中区域神经变性的定量评估。在这项研究中，我们量化了接触性运动运动员 （n = 185） 和非运动员对照 （n = 52） 在背外侧额叶皮层的沟深、中和回嵴内的三个关键神经退行性指标，包括皮质厚度、神经元密度和突触蛋白。与对照组相比，CTE 中沟内的皮质厚度和神经元密度降低 （p's < 0.05）。回嵴内突触蛋白的测量显示 α-突触核蛋白随着 CTE 阶段的减少 （p = 0.002） 和 PSD-95 密度的可变变化。调整年龄后，多元线性回归模型表明，接触性运动比赛的持续时间与脑沟内皮质变薄 （p = 0.001） 和神经元丢失 （p = 0.032） 之间存在很强的相关性。针对 tau 病理学进行调整的其他回归模型表明，在沟内，游戏持续时间主要通过 tau 病理学与神经元丢失相关。相比之下，游戏持续时间与皮质变薄的关联受 tau 病理学的影响最小。总体而言，CTE 与皮质萎缩和主要的脑沟神经变性有关。此外，接触性体育比赛的持续时间与神经退行性变的测量有关，神经退行性变在皮质沟中更为严重，并且可能通过 tau 依赖性和独立机制发生。