Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. Compared to typical high stage CTE, those with CSCTE had a similar age at death and years of contact sports participation and were less likely to carry apolipoprotein ε4 (p < 0.05). CSCTE had less overall tau pathology severity, but a proportional increase of disease burden in medial temporal lobe and brainstem regions compared to the neocortex (p’s < 0.001). CSCTE also had lower prevalence of comorbid neurodegenerative disease. Clinically, CSCTE participants were less likely to have dementia (p = 0.023) and had less severe cognitive difficulties (as reported by informants using the Functional Activities Questionnaire (FAQ); p < 0.001, meta-cognitional index T score; p = 0.002 and Cognitive Difficulties Scale (CDS); p < 0.001,) but had an earlier onset age of behavioral (p = 0.006) and Parkinsonian motor (p = 0.013) symptoms when compared to typical high stage CTE. Other comorbid tauopathies likely contributed in part to these differences: when cases with concurrent Alzheimer dementia or frontal temporal lobar degeneration with tau pathology were excluded, differences were largely retained, but only remained significant for FAQ (p = 0.042), meta-cognition index T score (p = 0.014) and age of Parkinsonian motor symptom onset (p = 0.046). Overall, CSCTE appears to be a distinct subtype of high stage CTE with relatively greater involvement of subcortical and brainstem regions and less severe cognitive symptoms.

慢性创伤性脑病 (CTE) 是一种由重复性头部撞击 (RHI) 引起的神经退行性疾病，病理学上定义为神经元磷酸化 tau 蛋白聚集在小血管周围并集中在脑沟深处。横断面研究表明，tau 包含物遵循一种刻板模式，在低阶段疾病中从新皮质开始，然后在高阶段 CTE 中累及内侧颞叶和皮质下区域，并产生显着的新皮质负担。在这里，我们定义了具有高 CTE 阶段和 tau 包涵体总体皮质负担较低（平均半定量值≤1）的大脑捐献者子集，并将其分类为皮质保留 CTE (CSCTE)。在 620 名经病理诊断患有 CTE 的脑捐献者中，66 名 (11%) 符合 CSCTE 标准。与典型的高级 CTE 相比，CSCTE 患者的死亡年龄和参与接触性运动的年数相似，并且携带载脂蛋白 ε4 的可能性较小( p  < 0.05)。与新皮质相比，CSCTE 的总体 tau 病理严重程度较低，但内侧颞叶和脑干区域的疾病负担成比例增加（p < 0.001）。CSCTE 合并神经退行性疾病的患病率也较低。临床上，CSCTE 参与者患痴呆症的可能性较小 ( p  = 0.023)，认知困难也较轻（根据知情者使用功能活动问卷 (FAQ) 的报告；p  < 0.001，元认知指数 T 评分；p  = 0.002 和认知困难量表 (CDS)；p < 0.001)，但 与典型的高级 CTE 相比，行为症状 ( p  = 0.006) 和帕金森运动症状 ( p = 0.013) 的发病年龄更早。其他共病 tau 病可能在一定程度上造成了这些差异：当排除并发阿尔茨海默痴呆或额颞叶变性伴 tau 病理学的病例时，差异在很大程度上保留，但仅在 FAQ ( p  = 0.042)、元认知指数 T 方面仍然显着。评分 ( p  = 0.014) 和帕金森运动症状发作年龄 ( p  = 0.046)。总体而言，CSCTE 似乎是高级 CTE 的一个独特亚型，皮质下和脑干区域受累相对较多，认知症状较轻。