Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, UK.
Acta Neuropathol. 2011 Oct;122(4):415-28. doi: 10.1007/s00401-011-0857-4. Epub 2011 Jul 21.
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.
许多最近的研究描述了 tau 阳性的球状少突胶质细胞包含物 (GOIs) 的病例，这些病例与进行性核上性麻痹 (PSP) 具有重叠的病理特征，但表现出运动神经元病 (MND) 和/或额颞叶痴呆 (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。我们描述了具有 GOIs 的两个病例的临床病理和生化特征：一个具有 MND 症状的病例，另一个具有 FTD 症状的病例。我们两个病例的组织学变化与他们的临床症状一致；MND 病例在初级运动皮层和皮质脊髓束中存在严重的神经退行性变，而 FTD 病例在额颞叶皮层及其相关白质中存在严重的受累。在两个病例中，免疫组织化学均显示出显著的 4 重复 (4R) tau 病理学，主要表现为 GOIs，但也存在于星形胶质细胞和神经元中。星形胶质细胞 tau 病理学在形态上与 PSP 所见相似，但与 PSP 不同的是，它始终对 Gallyas 银染色呈阴性。tau 特异性 Western blot 显示 68、64 和 35 kDa 条带，与 PSP 进一步重叠。这两个病例的潜在神经病理学特征相似，主要区别在于病理学的区域分布以及由此产生的临床症状和体征。神经胶质包含物的球形性质和星形胶质细胞中 tau 的非纤维性质是将其与 PSP 和其他 tau 病区分开来的特征。因此，我们提出球状神经胶质 tau 病作为一个包含性术语来分类这一新兴的 4R tau 病类别。
