Importance Globular glial tauopathies (GGTs), as defined by a consensus study in 2013, belong to the group of frontotemporal lobar degenerations and expand the spectrum of glial-predominant neurodegenerative diseases. Three neuropathological subtypes of GGT (types I-III) are characterized by phosphorylated tau-immunopositive inclusions that are predominantly in oligodendroglia and/or astroglia in the frontal, temporal, and/or precentral cortices. Type II is largely restricted to the corticospinal system. The low incidence of GGT (<10% of cases of frontotemporal lobar degeneration with tau pathology), together with its unusual combination of neuronal and nonneuronal pathology, has hindered identification and accurate diagnosis. This review collated clinical, demographic, neuropathological, and genetic data from 88 published GGT cases identified on PubMed to examine the association between GGT and frontotemporal dementia and associated disorders. Observations Among 88 patients with GGT (46 female [52.3%]; mean [SD] age at disease onset, 65 [11] years), 44 patients (50.0%) had idiopathic disease, and 21 patients (23.9%) had a variation in the microtubule-associated protein tau (MAPT) gene. Those with idiopathic GGT compared with those with a variation in MAPT had a mean (SD) age at symptom onset of 70 (8) years vs 54 (9) years and a mean (SD) disease duration of 7 (3) years vs 6 (3) years, respectively. A similar sex distribution was observed among patients with GGT; however, female patients were typically 6 years older at symptom onset than male patients (mean [SD] age, 68 [11] years vs 62 [11] years, respectively). Disease duration was similar in both sexes (mean [SD], 6 [3] years for women and 6 [4] years for men). The most common predominant clinical features were primary progressive aphasia (22 patients [25.0%]), behavioral-variant frontotemporal dementia (20 patients [22.7%]), upper motor neuron signs (11 patients [12.5%]), memory impairment (7 patients [8.0%]), and Richardson syndrome (7 patients [8.0%]). Although some demographic differences between GGT subtypes were identified, the predictive value of the clinical presentation was low, calling into question the need for neuropathological subtyping. Further neuropathological studies are needed to clarify whether GGT type II should be interpreted as atypical progressive supranuclear palsy or a separate entity. Few cases (7 patients [8.0%]) had coexisting proteinopathies. Conclusions and Relevance This review of the published data suggests an association between regional distribution of glial tau pathology and neuronal degeneration. Targeting glial tau accumulation or sustaining their neuron-supportive function might require different therapeutic or neuroprotective strategies and more accurate preclinical models to explore disease mechanisms and track progression. Emerging data support the important role of glia in the pathogenesis of neurodegenerative disorders, highlighting the need to raise awareness of GGT in clinical and research settings.

中文翻译：

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球状胶质细胞 Tauopathies 与额颞叶痴呆之间的关联——扩大胶质中心疾病的范围：综述。

重要性 2013 年一项共识研究定义的球状胶质细胞 tau蛋白病 (GGT) 属于额颞叶变性组，并扩大了以胶质为主的神经退行性疾病的范围。GGT 的三种神经病理学亚型（I-III 型）的特点是磷酸化 tau 免疫阳性包涵体，主要存在于额叶、颞叶和/或中央前皮质的少突胶质细胞和/或星形胶质细胞中。II 型主要局限于皮质脊髓系统。GGT 的低发病率（<10% 的额颞叶变性伴有 tau 病理），连同其不寻常的神经元和非神经元病理组合，阻碍了识别和准确诊断。本综述整理了临床、人口统计学、神经病理学、以及来自 PubMed 上确定的 88 例已发表 GGT 病例的遗传数据，以检查 GGT 与额颞叶痴呆及相关疾病之间的关联。观察 88 名 GGT 患者（46 名女性 [52.3%]；发病时的平均 [SD] 年龄，65 [11] 岁），44 名患者（50.0%）患有特发性疾病，21 名患者（23.9%）有变异在微管相关蛋白 tau (MAPT) 基因中。与 MAPT 变异的患者相比，特发性 GGT 患者的平均 (SD) 发病年龄为 70 (8) 岁 vs 54 (9) 岁，平均 (SD) 疾病持续时间为 7 (3) 年 vs 6 年(3) 年，分别。在 GGT 患者中观察到相似的性别分布；然而，女性患者在出现症状时通常比男性患者大 6 岁（平均 [SD] 年龄，分别为 68 [11] 岁和 62 [11] 岁）。两性的疾病持续时间相似（平均 [SD]，女性为 6 [3] 年，男性为 6 [4] 年）。最常见的主要临床特征是原发性进行性失语（22 例 [25.0%]）、行为变异性额颞叶痴呆（20 例 [22.7%]）、上运动神经元体征（11 例 [12.5%]）、记忆障碍（7患者 [8.0%]) 和理查森综合征 (7 患者 [8.0%])。尽管确定了 GGT 亚型之间的一些人口统计学差异，但临床表现的预测价值很低，从而质疑神经病理学亚型的必要性。需要进一步的神经病理学研究来阐明 GGT II 型是否应解释为非典型进行性核上性麻痹或单独的实体。少数病例（7 名患者 [8.0%]）合并有蛋白质病。结论和相关性 对已发表数据的审查表明神经胶质 tau 病理的区域分布与神经元变性之间存在关联。针对胶质细胞 tau 积累或维持其神经元支持功能可能需要不同的治疗或神经保护策略和更准确的临床前模型来探索疾病机制和跟踪进展。新兴数据支持神经胶质细胞在神经退行性疾病发病机制中的重要作用，强调需要在临床和研究环境中提高对 GGT 的认识。针对胶质细胞 tau 积累或维持其神经元支持功能可能需要不同的治疗或神经保护策略和更准确的临床前模型来探索疾病机制和跟踪进展。新兴数据支持神经胶质细胞在神经退行性疾病发病机制中的重要作用，强调需要在临床和研究环境中提高对 GGT 的认识。针对胶质细胞 tau 积累或维持其神经元支持功能可能需要不同的治疗或神经保护策略和更准确的临床前模型来探索疾病机制和跟踪进展。新兴数据支持神经胶质细胞在神经退行性疾病发病机制中的重要作用，强调需要在临床和研究环境中提高对 GGT 的认识。