The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene
The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene
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DOI：
10.1093/brain/awl271
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发表时间：
2006-11-01
期刊：
影响因子：
14.5
通讯作者：
Feldman, Howard H.
中科院分区：
文献类型：
--
作者：
Mackenzie, Ian R. A.;Baker, Matt;Feldman, Howard H.
额颞叶痴呆（FTD）中最常见的病理是tau蛋白阴性、泛素免疫反应性（ub-ir）神经元包涵体（FTLD-U）。最近，我们确定了颗粒蛋白前体（PGRN）基因突变是与17号染色体连锁的常染色体显性FTLD-U的原因。在这里，我们描述了来自6个不同家族的13例患者的神经病理学，每个患者都患有由不同PGRN突变引起的FTD。最一致的特征是在新皮层和纹状体中存在亚红外豆状核神经元核内包涵体（NII）。此外，新皮质显示中度至重度浅表层海绵状增生、慢性退行性变化、ub-ir神经突和明确的ub-ir神经元胞质内含物（NCI）。在纹状体，有许多ub-ir神经突起。海马区的NCI通常呈颗粒状。相比之下，没有PGRN突变的家族性FTLD-U病例没有NII，新皮质和纹状体病理不太严重，海马NCI更常见。8例遗传分析不可用的病例也有NII，总体病理学与已证实突变的病例相似。我们的FTLD-U无NII的病例均未显示出与有突变的病例相同的病理模式。这些结果表明，PGRN突变引起的FTD具有可识别的病理学，最具特征的特征是ub-ir NII。
The most common pathology in frontotemporal dementia (FTD) is tau-negative, ubiquitin-immunoreactive (ub-ir) neuronal inclusions (FTLD-U). Recently, we identified mutations in the progranulin (PGRN) gene as the cause of autosomal dominant FTLD-U linked to chromosome 17. Here, we describe the neuropathology in 13 patients from 6 different families, each with FTD caused by a different PGRN mutation. The most consistent feature was the presence of ub-ir lentiform neuronal intranuclear inclusions (NII) in the neocortex and striatum. In addition, the neocortex showed moderate-to-severe superficial laminar spongiosis, chronic degenerative changes, ub-ir neurites and well-defined ub-ir neuronal cytoplasmic inclusions (NCI). In the striatum, there were numerous ub-ir neurites. NCI in the hippocampus usually had a granular appearance. In contrast, familial FTLD-U cases without PGRN mutations had no NII, less severe neocortical and striatal pathology and hippocampal NCI that were more often solid. Eight cases in which genetic analysis was not available also had NII and an overall pathology similar to those with proven mutations. None of our cases of FTLD-U without NII showed the same pattern of pathology as those with mutations. These findings suggest that FTD caused by PGRN mutations has a recognizable pathology with the most characteristic feature being ub-ir NII.