Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease, including chronic traumatic encephalopathy (CTE). Preliminary consensus criteria define the pathognomonic lesion of CTE as patchy tau pathology within neurons and astrocytes at the depths of cortical sulci. However, the specific tau isoform composition and post-translational modifications in CTE remain largely unexplored. Using immunohistochemistry, we performed tau phenotyping of CTE neuropathologies and compared this to a range of tau pathologies, including Alzheimer's disease, primary age-related tauopathy, ageing-related tau astrogliopathy and multiple subtypes of frontotemporal lobar degeneration with tau inclusions. Cases satisfying preliminary consensus diagnostic criteria for CTE neuropathological change (CTE-NC) were identified (athletes, n = 10; long-term survivors of moderate or severe TBI, n = 4) from the Glasgow TBI Archive and Penn Neurodegenerative Disease Brain Bank. In addition, material from a range of autopsy-proven ageing-associated and primary tauopathies in which there was no known history of exposure to TBI was selected as non-injured controls (n = 32). Each case was then stained with a panel of tau antibodies specific for phospho-epitopes (PHF1, CP13, AT100, pS262), microtubule-binding repeat domains (3R, 4R), truncation (Tau-C3) or conformation (GT-7, GT-38) and the extent and distribution of staining assessed. Cell types were confirmed with double immunofluorescent labelling. Results demonstrate that astroglial tau pathology in CTE is composed of 4R-immunoreactive thorn-shaped astrocytes, echoing the morphology and immunophenotype of astrocytes encountered in ageing-related tau astrogliopathy. In contrast, neurofibrillary tangles of CTE contain both 3R and 4R tau, with post-translational modifications and conformations consistent with Alzheimer's disease and primary age-related tauopathy. Our observations establish that the astroglial and neurofibrillary tau pathologies of CTE are phenotypically distinct from each other and recapitulate the tau immunophenotypes encountered in ageing and Alzheimer's disease. As such, the immunohistochemical distinction of CTE neuropathology from other mixed 3R/4R tauopathies of Alzheimer's disease and ageing may rest solely on the pattern and distribution of pathology.

中文翻译：

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慢性创伤性脑病中的Tau免疫表型概括了衰老和阿尔茨海默氏病的表型。

颅脑外伤（TBI）是神经退行性疾病（包括慢性创伤性脑病（CTE））的危险因素。初步的共识标准将CTE的病理性病变定义为皮质沟深处神经元和星形胶质细胞内的斑块状tau病理。然而，在CTE中特定的tau异构体组成和翻译后修饰仍未开发。使用免疫组织化学，我们对CTE神经病理进行了tau表型分析，并将其与一系列tau病理进行了比较，包括阿尔茨海默氏病，原发性年龄相关的tauopathy，与衰老相关的tau星形神经胶质病以及带有tau夹杂物的额颞叶变性的多种亚型。确定满足CTE神经病理学改变的初步共识诊断标准的病例（运动员，n = 10； n = 10； n = 10）。格拉斯哥TBI档案馆和宾夕法尼亚神经退行性疾病脑库的中度或重度TBI的长期幸存者（n = 4）。此外，选择了一系列经尸检证实的与衰老相关的原发性疾病，其中没有已知的TBI暴露史的材料被选为非伤害性对照（n = 32）。然后，每种情况都用一组针对磷酸表位（PHF1，CP13，AT100，pS262），微管结合重复结构域（3R，4R），截短（Tau-C3）或构象（GT-7， GT-38）以及染色的程度和分布进行评估。通过双重免疫荧光标记确认了细胞类型。结果表明CTE中的星形胶质头tau病理由4R免疫反应性刺状星形胶质细胞组成，与衰老相关的tau星形胶质细胞增生症中星形胶质细胞的形态和免疫表型相呼应。相比之下，CTE的神经原纤维缠结包含3R和4R tau，翻译后修饰和构象与阿尔茨海默氏病和原发性年龄相关的tauopathy一致。我们的观察结果表明，CTE的星形胶质和神经原纤维tau病理在表型上彼此不同，并概括了在衰老和阿尔茨海默氏病中遇到的tau免疫表型。因此，CTE神经病理学与阿尔茨海默氏病和衰老的其他3R / 4R混合型其他病理学的免疫组织化学区别可能仅取决于病理学的模式和分布。翻译后修饰和构象与阿尔茨海默氏病和原发性年龄相关的tauopathy一致。我们的观察结果表明，CTE的星形胶质和神经原纤维tau病理在表型上彼此不同，并概括了在衰老和阿尔茨海默氏病中遇到的tau免疫表型。因此，CTE神经病理学与阿尔茨海默氏病和衰老的其他3R / 4R混合型其他病理学的免疫组织化学区别可能仅取决于病理学的模式和分布。翻译后修饰和构象与阿尔茨海默氏病和原发性年龄相关的tauopathy一致。我们的观察结果表明，CTE的星形胶质和神经原纤维tau病理在表型上彼此不同，并概括了在衰老和阿尔茨海默氏病中遇到的tau免疫表型。因此，CTE神经病理学与阿尔茨海默氏病和衰老的其他3R / 4R混合型其他病理学的免疫组织化学区别可能仅取决于病理学的模式和分布。我们的观察结果表明，CTE的星形胶质和神经原纤维tau病理在表型上彼此不同，并概括了在衰老和阿尔茨海默氏病中遇到的tau免疫表型。因此，CTE神经病理学与阿尔茨海默氏病和衰老的其他3R / 4R混合型其他病理学的免疫组织化学区别可能仅取决于病理学的模式和分布。我们的观察结果表明，CTE的星形胶质和神经原纤维tau病理在表型上彼此不同，并概括了在衰老和阿尔茨海默氏病中遇到的tau免疫表型。因此，CTE神经病理学与阿尔茨海默氏病和衰老的其他3R / 4R混合型其他病理学的免疫组织化学区别可能仅取决于病理学的模式和分布。