Tau Pathology in Chronic Traumatic Encephalopathy is Primarily Neuronal.
Tau Pathology in Chronic Traumatic Encephalopathy is Primarily Neuronal.
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DOI：
10.1093/jnen/nlac065
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发表时间：
2022-09-19
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
每年有数百万人通过接触性运动、军事爆炸和人际暴力暴露于重复性头部撞击（RHI）。RHI是发展慢性创伤性脑病（CTE）的主要风险因素，CTE是一种神经退行性tau蛋白病。最近的共识标准将CTE中的特异性病变定义为神经元聚集体中血管周围的过度磷酸化tau（p-tau）。星形胶质细胞p-tau是一个不一致的支持特征，本身不能诊断CTE。本研究定量分析了150名年龄在21岁至80岁之间，无共病病理的CTE患者死后背外侧额叶皮质中p-tau病理的空间和细胞分布。在灰质沟、嵴、软膜下区和病理性CTE病变内定量p-Tau免疫反应细胞。在所有皮质区域发现神经元p-tau显著多于星形胶质细胞p-tau（p < 0.0001）。脑沟星形胶质细胞p-tau主要（75%，p < 0.0001）定位于软膜下区域，作为棘状星形胶质细胞，一种与年龄相关的tau星形胶质细胞病。神经元p-tau与年龄、RHI暴露年数和CTE严重程度显著相关;星形胶质细胞p-tau病理学仅与年龄显著相关。这些发现强烈支持神经元变性作为CTE的驱动特征，并将有助于为未来的研究和用于检测CTE中神经元变性的流体生物标志物的开发提供信息。
Millions of individuals are exposed to repetitive head impacts (RHI) each year through contact sports, military blast, and interpersonal violence. RHI is the major risk factor for developing chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. Recent consensus criteria defined the pathognomonic lesion in CTE as perivascular, hyperphosphorylated tau (p-tau) in neuronal aggregates. Astroglial p-tau is an inconsistent supporting feature and not in itself diagnostic of CTE. This study quantitated the spatial and cellular distribution of p-tau pathology in postmortem dorsolateral frontal cortex of 150 individuals with CTE, from ages 21 to 80 years old, without comorbid pathology. p-Tau-immunoreactive cells were quantitated in the gray matter sulcus, crest, subpial region, and within pathognomonic CTE lesions. Significantly more neuronal p-tau than astrocytic p-tau was found across all cortical regions (p < 0.0001). Sulcal astrocytic p-tau was primarily (75%, p < 0.0001) localized to subpial regions as thorn-shaped astrocytes, a form of age-related tau astrogliopathy. Neuronal p-tau was significantly associated with age, years of RHI exposure, and CTE severity; astrocytic p-tau pathology was only significantly associated with age. These findings strongly support neuronal degeneration as a driving feature of CTE and will help inform future research and the development of fluid biomarkers for the detection of neuronal degeneration in CTE.
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影响因子：
7.1
作者：
Bachstetter AD;Garrett FG;Jicha GA;Nelson PT
通讯作者：
Nelson PT
影响因子：
3.2
作者：
Bieniek KF;Cairns NJ;Crary JF;Dickson DW;Folkerth RD;Keene CD;Litvan I;Perl DP;Stein TD;Vonsattel JP;Stewart W;Dams-O'Connor K;Gordon WA;Tripodis Y;Alvarez VE;Mez J;Alosco ML;McKee AC;TBI/CTE Research Group
通讯作者：
TBI/CTE Research Group
影响因子：
3.2
作者：
Doherty, Colin P.;O'Keefe, Eoin;Campbell, Matthew
通讯作者：
Campbell, Matthew
影响因子：
12.7
作者：
Kovacs GG;Ferrer I;Grinberg LT;Alafuzoff I;Attems J;Budka H;Cairns NJ;Crary JF;Duyckaerts C;Ghetti B;Halliday GM;Ironside JW;Love S;Mackenzie IR;Munoz DG;Murray ME;Nelson PT;Takahashi H;Trojanowski JQ;Ansorge O;Arzberger T;Baborie A;Beach TG;Bieniek KF;Bigio EH;Bodi I;Dugger BN;Feany M;Gelpi E;Gentleman SM;Giaccone G;Hatanpaa KJ;Heale R;Hof PR;Hofer M;Hortobágyi T;Jellinger K;Jicha GA;Ince P;Kofler J;Kövari E;Kril JJ;Mann DM;Matej R;McKee AC;McLean C;Milenkovic I;Montine TJ;Murayama S;Lee EB;Rahimi J;Rodriguez RD;Rozemüller A;Schneider JA;Schultz C;Seeley W;Seilhean D;Smith C;Tagliavini F;Takao M;Thal DR;Toledo JB;Tolnay M;Troncoso JC;Vinters HV;Weis S;Wharton SB;White CL 3rd;Wisniewski T;Woulfe JM;Yamada M;Dickson DW
通讯作者：
Dickson DW
影响因子：
7.1
作者：
Ameen-Ali KE;Bretzin A;Lee EB;Folkerth R;Hazrati LN;Iacono D;Keene CD;Kofler J;Kovacs GG;Nolan A;Perl DP;Priemer DS;Smith DH;Wiebe DJ;Stewart W;CONNECT-TBI Investigators
通讯作者：
CONNECT-TBI Investigators