A morphometric study of the spatial patterns of TDP-43 immunoreactive neuronal inclusions in frontotemporal lobar degeneration (FTLD) with progranulin (GRN) mutation
A morphometric study of the spatial patterns of TDP-43 immunoreactive neuronal inclusions in frontotemporal lobar degeneration (FTLD) with progranulin (GRN) mutation
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DOI：
10.14670/hh-26.185
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发表时间：
2011-02-01
影响因子：
2
通讯作者：
Cairns, Nigel J.
中科院分区：
文献类型：
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作者：
Armstrong, Richard A.;Cairns, Nigel J.
颗粒体蛋白前体 (GRN) 基因突变是家族性额颞叶变性伴 43kDa 的相互作用反应 (TAR) DNA 结合蛋白 (TDP-43) 蛋白病 (FTLD-TDP) 的主要原因。我们使用形态测量方法和空间模式分析，研究了 8 例伴有 GRN 突变的 FTLD-TDP 病例额叶和颞叶组织学切片中 TDP-43 免疫反应性神经元细胞质包涵体 (NCI) 和神经元核内包涵体 (NII) 的空间模式。在新皮质区域，NCI呈簇状分布，且簇有规律地平行于软脑膜分布； 58% 的分析区域表现出这种模式。 NII 在 35% 的地区呈规则分布的集群，但在许多地区也呈随机分布。在新皮质区域，NCI和NII的规则簇的尺寸为400-800μm，接近皮质-皮质投影的模块柱的尺寸，分别占31%和36%的区域。 NCI 和 NII 还在海马 CA1/2 区和齿状回中表现出规则间隔的聚集。 NCI 和 NII 的簇在空间上不相关。数据表明，GRN 突变的 FTLD-TDP 中皮质-皮质和皮质-海马通路发生退化，NCI 和 NII 影响不同的神经元簇。
Mutations of the progranulin (GRN) gene are a major cause of familial frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP). We studied the spatial patterns of TDP-43 immunoreactive neuronal cytoplasmic inclusions (NCI) and neuronal intranuclear inclusions (NII) in histological sections of the frontal and temporal lobe in eight cases of FTLD-TDP with GRN mutation using morphometric methods and spatial pattern analysis. In neocortical regions, the NCI were clustered and the clusters were regularly distributed parallel to the pia mater; 58% of regions analysed exhibiting this pattern. The NII were present in regularly distributed clusters in 35% of regions but also randomly distributed in many areas. In neocortical regions, the sizes of the regular clusters of NCI and NII were 400-800 mu m, approximating to the size of the modular columns of the cortico-cortical projections, in 31% and 36% of regions respectively. The NCI and NII also exhibited regularly spaced clustering in sectors CA1/2 of the hippocampus and in the dentate gyrus. The clusters of NCI and NII were not spatially correlated. The data suggest degeneration of the cortico-cortical and cortico-hippocampal pathways in FTLD-TDP with GRN mutation, the NCI and NII affecting different clusters of neurons.