A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3
A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3
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DOI：
10.1097/nen.0b013e3181567f02
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发表时间：
2007-10-01
影响因子：
3.2
通讯作者：
Isaacs, Adrian M.
中科院分区：
文献类型：
--
作者：
Holm, Ida Elisabeth;Englund, Elisabet;Isaacs, Adrian M.
以前曾报道过一个丹麦大家族，其中常染色体显性额颞叶痴呆（FTD）与3号染色体（FTD-3）遗传连锁。最近在CHMP 2B基因中发现了一种突变，可能是导致该家族疾病的原因。由于其神经病理学结果，FTD-3最初被归类为额颞叶变性的一种亚型，称为“缺乏独特组织病理学的痴呆”。“我们现在报告对这个家庭的神经病理学变化的重新评估。4名受影响家庭成员的尸检材料可供检查。大体检查显示全身性皮质萎缩，其中额叶和颞叶皮质最为严重。显微镜检查显示皮层神经元丢失。第11层的微空泡化、轻度神经胶质增生和深层白色物质的脱髓鞘。α-突触核蛋白、朊病毒蛋白、神经丝蛋白和tau蛋白的免疫组织化学染色结果不显著。在所有4例病例中，海马齿状颗粒层均存在数量不等的小而圆的泛素阳性胞质包涵体。在额叶和颞叶皮质神经元中也发现了罕见的泛素阳性包涵体。这些包涵体对p62也呈阳性，但对TDP-43不呈阳性。在海马和新皮质中发现泛素和p62阳性、TDP-43阴性的细胞质包涵体，表明FTD-3的神经病理学重新分类为额颞叶变性的一种独特亚型，其中泛素阳性包涵体为TDP-43阴性。
A large Danish family has previously been reported in which autosomal dominant frontotemporal dementia (FTD) is genetically linked to chromosome 3 (FTD-3). A mutation was recently identified in the CHMP2B gene that is probably responsible for causing disease in this family. Because of its neuropathologic findings, FTD-3 was originally categorized as a subtype of frontotemporal lobar degeneration, termed "dementia lacking distinctive histopathology." We now report a reevaluation of the neuropathologic changes in this family. Postmortem material from 4 affected family members was available for examination. Gross examination revealed generalized cortical atrophy that was most severe in frontal and temporal cortices. Microscopy showed loss of cortical neurons. microvacuolation of layer 11, mild gliosis, and demyelination of the deep white matter. Results of immunohistochemical staining for alpha-synuclein, prion protein, neurofilament, and tau protein were unremarkable. Variable numbers of small, round, ubiquitin-positive cytoplasmic inclusions were present in the dentate granule layer of the hippocampus in all 4 cases. Rare ubiquitin-positive inclusions were also found in frontal and temporal cortical neurons. These inclusions were also positive for p62 but not for TDP-43. The finding of ubiquitin- and p62-positive, TDP-43-neaative cytoplasmic inclusions in the hippocampus and neocortex suggests reclassification of the neuropathology of FTD-3 as a unique subtype of frontotemporal lobar degeneration with ubiquitin-positive inclusions that are TDP-43 -negative.