TDP-43-negative FTLD-U is a significant new clinico-pathological subtype of FTLD
TDP-43-negative FTLD-U is a significant new clinico-pathological subtype of FTLD
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DOI：
10.1007/s00401-008-0395-x
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发表时间：
2008-08-01
影响因子：
12.7
通讯作者：
Neumann, Manuela
中科院分区：
文献类型：
--
作者：
Roeber, Sigrun;Mackenzie, Ian R. A.;Neumann, Manuela
额颞叶变性伴泛素阳性包涵体（FTLD-U）是额颞叶痴呆最常见的神经病理亚型。虽然TDP-43是大多数FTLD-U病例的病理蛋白，但最近报道了少数TDP-43阴性的FTLD-U病例。为了确定tdp -43阴性FTLD-U的频率和定义临床病理谱，我们重新评估了44例先前诊断为FTLD-U或痴呆的患者，这些患者缺乏独特的组织病理学。我们通过免疫组化鉴定出9例（20%）FTLD-U病理TDP-43阴性，生化分析证实病理TDP-43缺失。所有患者均表现为散发性早发额颞叶痴呆，主要表现为行为和人格改变。除了泛素阳性的神经元胞质包涵体外，最有趣的神经病理特征是泛素阳性的神经元核内包涵体（NIIs）的存在，通常在新皮层、海马、脑干和脊髓中呈现弯曲或扭曲的形态。双标记免疫荧光显示这些NIIs具有不同寻常和独特的免疫反应性，具有泛素免疫反应性，但缺乏p62标记。高度一致的临床和神经病理表型支持tdp -43阴性FTLD- u应被视为新的临床病理FTLD实体的概念。
Frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) is the most common neuropathological subtype of frontotemporal dementias. While TDP-43 is the pathologic protein in the majority of FTLD-U cases, small numbers of cases have recently been reported with TDP-43-negative FTLD-U pathology. To determine the frequency and to define the clinico-pathological spectrum of TDP-43-negative FTLD-U, we re-evaluated 44 cases with a previous diagnosis of FTLD-U or dementia lacking distinctive histopathology. We identified nine cases (20%) with TDP-43-negative FTLD-U pathology by immunohistochemistry and confirmed the absence of pathological TDP-43 by biochemical analysis. All patients presented with sporadic early-onset frontotemporal dementia with predominant behavioral and personality changes. Besides ubiquitin-positive neuronal cytoplasmic inclusions, the most intriguing neuropathological feature was the presence of ubiquitin-positive neuronal intranuclear inclusions (NIIs), often with curved or twisted morphology, in the neocortex, hippocampus, brainstem, and spinal cord. Double-label immunofluorescence revealed an unusual and distinct immunoreactivity profile for these NIIs, with ubiquitin-immunoreactivity, but absence of p62 labeling. The highly consistent clinical and neuropathological phenotype supports the concept that TDP-43-negative FTLD-U should be considered as a new clinicopathological FTLD entity.