Spinal Cord and Brain Injury Research Center, University of Kentucky, 741 S. Limestone St., Lexington, KY, 40536, USA.
Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
Acta Neuropathol Commun. 2021 Mar 23;9(1):49. doi: 10.1186/s40478-021-01152-3.
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.
星形胶质细胞内存在错误折叠的磷酸化 tau 蛋白的细胞内堆积物已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。人们越来越意识到，星形胶质细胞内的 tau 包含物在 70 岁以上人群的大脑中也相对常见-影响大约三分之一的尸检个体。与年龄相关的 tau 星形胶质细胞病 (ARTAG) 的病理标志物包括在软膜下、室管膜下、血管周围和白质区域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。CTE 和 ARTAG 具有分子和组织病理学特征，表明与创伤相关的机制可能易患 tau 星形胶质细胞病。目前，很少有实验系统可以研究星形胶质细胞-tau 聚集的病理生物学，但人类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）在手术后数十年与局部性 ARTAG 样神经病理学相关，这表明任何类型的慢性脑损伤都可能易患后期生活中的 ARTAG。为了在不同的背景下研究这个想法，我们报告了两名中年男性的临床和病理特征，他们在尸检时患有大 (>6cm 最大尺寸) 蛛网膜囊肿，这些囊肿通过慢性机械压力物理性地移位并损伤了受试者的左侧颞叶。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局和神经病理学发现不同。我们回顾了针对脑损伤的 ARTAG 证据，并讨论了星形胶质细胞 tau 包含物的位置和分子特性如何改变驻留星形胶质细胞的生理学。这些病例和文献综述表明了慢性脑创伤后星形胶质细胞中 tau 聚集的可能机制。
