Space-occupying brain lesions, trauma-related tau astrogliopathy, and ARTAG: a report of two cases and a literature review.
Space-occupying brain lesions, trauma-related tau astrogliopathy, and ARTAG: a report of two cases and a literature review.
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DOI：
10.1186/s40478-021-01152-3
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发表时间：
2021-03-23
影响因子：
7.1
通讯作者：
Nelson PT
中科院分区：
文献类型：
--
作者：
Bachstetter AD;Garrett FG;Jicha GA;Nelson PT
在晚期慢性创伤性脑病（CTE）和其他神经退行性疾病中观察到星形胶质细胞细胞内错误折叠磷酸化tau蛋白的积累。越来越多的人意识到星形胶质细胞tau蛋白包涵体在70岁以上的人的大脑中也相对常见，影响了大约三分之一的尸检个体。衰老相关的tau星形胶质细胞病（ARTAG）的病理标志包括软膜下、室管膜下、血管周围和白色物质区域中的刺状星形胶质细胞（TSA）内的磷酸化tau蛋白，而颗粒状模糊星形胶质细胞通常见于灰质中。CTE和ARTAG具有共同的分子和组织病理学特征，表明创伤相关机制可能易导致tau星形胶质细胞病的发生。目前研究星形胶质细胞-tau聚集病理生物学的实验系统很少，但人体研究最近取得了进展。例如，脑白质切开术（也称为脑叶切开术）与外科脑损伤后数十年的局部ARTAG样神经病理学相关，表明任何类型的慢性脑损伤都可能使老年人易患ARTAG。为了在不同的背景下检验这一观点，我们报告了两名中年男子的临床和病理特征，他们因慢性机械应力导致受试者左颞叶的物理移位和损伤而进行尸检，患有大的（最大尺寸> 6 cm）蛛网膜囊肿。尽管蛛网膜囊肿的大小和位置相似，但这些个体的神经学结果和神经病理学结果不同。我们回顾了ARTAG对脑损伤反应的证据，并讨论了星形胶质细胞tau蛋白包涵体的位置和分子特性如何改变常驻星形胶质细胞的生理学。这些病例和文献综述指出了星形胶质细胞中tau聚集对慢性脑创伤的反应的可能机制。
Astrocytes with intracellular accumulations of misfolded phosphorylated tau protein have been observed in advanced-stage chronic traumatic encephalopathy (CTE) and in other neurodegenerative conditions. There is a growing awareness that astrocytic tau inclusions are also relatively common in the brains of persons over 70 years of age—affecting approximately one-third of autopsied individuals. The pathologic hallmarks of aging-related tau astrogliopathy (ARTAG) include phosphorylated tau protein within thorn-shaped astrocytes (TSA) in subpial, subependymal, perivascular, and white matter regions, whereas granular-fuzzy astrocytes are often seen in gray matter. CTE and ARTAG share molecular and histopathologic characteristics, suggesting that trauma-related mechanism(s) may predispose to the development of tau astrogliopathy. There are presently few experimental systems to study the pathobiology of astrocytic-tau aggregation, but human studies have made recent progress. For example, leucotomy (also referred to as lobotomy) is associated with a localized ARTAG-like neuropathology decades after the surgical brain injury, suggesting that chronic brain injury of any type may predispose to later life ARTAG. To examine this idea in a different context, we report clinical and pathologic features of two middle-aged men who came to autopsy with large (> 6 cm in greatest dimension) arachnoid cysts that had physically displaced and injured the subjects’ left temporal lobes through chronic mechanical stress. Despite the similarity of the size and location of the arachnoid cysts, these individuals had dissimilar neurologic outcomes and neuropathologic findings. We review the evidence for ARTAG in response to brain injury, and discuss how the location and molecular properties of astroglial tau inclusions might alter the physiology of resident astrocytes. These cases and literature review point toward possible mechanism(s) of tau aggregation in astrocytes in response to chronic brain trauma.
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影响因子：
34.7
作者：
Clarke, Laura E.;Barres, Ben A.
通讯作者：
Barres, Ben A.
影响因子：
3.3
作者：
Colnaghi L;Rondelli D;Muzi-Falconi M;Sertic S
通讯作者：
Sertic S
影响因子：
9.3
作者：
Early, Alexandria N.;Gorman, Amy A.;Morganti, Josh M.
通讯作者：
Morganti, Josh M.
DOI：
10.1073/pnas.1507125112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
通讯作者：
Quake SR
影响因子：
29
作者：
Gibbons GS;Lee VMY;Trojanowski JQ
通讯作者：
Trojanowski JQ