Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer's disease
Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer's disease
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DOI：
10.1093/brain/awaa071
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发表时间：
2020-05-01
期刊：
影响因子：
14.5
通讯作者：
Johnson, Victoria E.
中科院分区：
文献类型：
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作者：
Arena, John D.;Smith, Douglas H.;Johnson, Victoria E.
创伤性脑损伤（TBI）是神经退行性疾病（包括慢性创伤性脑病（CTE））的危险因素。初步共识标准将CTE的特异性病变定义为皮层沟深处神经元和星形胶质细胞内的斑片状tau病变。然而，CTE中的特定tau亚型组成和翻译后修饰在很大程度上仍未被探索。使用免疫组织化学，我们进行了CTE神经病理学的tau表型分析，并将其与一系列tau病理学进行了比较，包括阿尔茨海默病，原发性年龄相关性tau病变，年龄相关性tau星形胶质细胞病变和多种亚型的额颞叶变性与tau夹杂物。从格拉斯哥TBI档案和宾夕法尼亚州神经退行性疾病脑库中确定了满足CTE神经病理学变化（CTE-NC）初步共识诊断标准的病例（运动员，n = 10;中度或重度TBI的长期存活者，n = 4）。此外，选择来自一系列尸检证实的衰老相关和原发性tau蛋白病的材料作为非损伤对照（n = 32），其中没有已知的TBI暴露史。然后用一组特异于磷酸化表位（PHF 1、CP 13、AT 100、pS262）、微管结合重复结构域（3R、4 R）、截短（Tau-C3）或构象（GT-7、GT-38）的tau抗体对每个病例进行染色，并评估染色的程度和分布。用双重免疫荧光标记确认细胞类型。结果表明，CTE中的星形胶质细胞tau病理学由4 R免疫反应性棘状星形胶质细胞组成，与年龄相关的tau星形胶质细胞病中遇到的星形胶质细胞的形态学和免疫表型相呼应。相反，CTE的神经元缠结含有3R和4 R tau，具有与阿尔茨海默病和原发性年龄相关的tau蛋白病一致的翻译后修饰和构象。我们的观察结果表明，CTE的星形胶质细胞和神经胶质细胞tau病理学在表型上彼此不同，并概括了衰老和阿尔茨海默病中遇到的tau免疫表型。因此，CTE神经病理学与阿尔茨海默病和衰老的其他混合3R/4 R tau蛋白病的免疫组织化学区别可能仅取决于病理学的模式和分布。
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.