Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathies
Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathies
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DOI：
10.1007/s00401-011-0857-4
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发表时间：
2011-10-01
影响因子：
12.7
通讯作者：
Revesz, Tamas
中科院分区：
文献类型：
--
作者：
Ahmed, Zeshan;Doherty, Karen M.;Revesz, Tamas
最近的一些研究描述了tau阳性的球状少突胶质包涵体(GOIS)病例，这些病例的病理特征与进行性核上性瘫痪(PSP)重叠，但表现为运动神经元病(MND)和/或额颞部痴呆(FTD)的临床特征。这两种临床表型已经独立发表，因此，被认为是不同的疾病实体。我们描述了两例GOIS的临床病理和生化特征：一例临床症状提示为MND，另一例为FTD。我们的两个病例的组织学改变与他们的临床症状相一致；MND病例的初级运动皮质和皮质脊髓束有严重的神经变性，而FTD病例有严重的额颞叶皮质和伴发的白质受累。两例免疫组织化学均显示明显的4-重复(4R)tau病变，主要表现为GOI，但也存在于星形胶质细胞和神经元中。星形细胞tau病理在形态上与PSP相似，但与之相反，Galyas银染始终为阴性。Tau特异的Western blotting显示68条、和35 kDa条带，显示与PSP进一步重叠。这两个病例的基本神经病理特征相似，主要的差异与病理的区域分布和由此导致的临床症状和体征有关。星形胶质细胞中胶质包涵体的球状和tau的非纤维性是区别于PSP和其他tau病的特征。因此，我们建议将球状神经胶质瘤作为一个包罗万象的术语来分类这类新兴的4R神经元瘤。
A number of recent studies have described cases with tau-positive globular oligodendroglial inclusions (GOIs) and such cases have overlapping pathological features with progressive supranuclear palsy (PSP), but present with clinical features of motor neuron disease (MND) and/or frontotemporal dementia (FTD). These two clinical phenotypes have been published independently and as a result, have come to be considered as distinct disease entities. We describe the clinicopathological and biochemical features of two cases with GOIs: one with clinical symptoms suggestive of MND and the other with FTD. Histological changes in our two cases were consistent with their clinical symptoms; the MND case had severe neurodegeneration in the primary motor cortex and corticospinal tract, whereas the FTD case had severe involvement of the frontotemporal cortices and associated white matter. Immunohistochemistry in both cases revealed significant 4-repeat (4R) tau pathology primarily in the form of GOIs, but also in astrocytes and neurons. Astrocytic tau pathology was morphologically similar to that seen in PSP, but in contrast was consistently negative for Gallyas silver staining. Tau-specific western blotting revealed 68, 64 and 35 kDa bands, showing further overlap with PSP. The underlying neuropathological features of these two cases were similar, with the major difference relating to the regional distribution of pathology and resulting clinical symptoms and signs. The globular nature of glial inclusions and the non-fibrillar properties of tau in astrocytes are characteristic features that allow them to be distinguished from PSP and other tauopathies. We, therefore, propose the term globular glial tauopathy as an encompassing term to classify this emerging class of 4R tauopathy.