Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation
Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation
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DOI：
10.1007/s00401-005-1079-4
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发表时间：
2005-11-01
影响因子：
12.7
通讯作者：
Mann, DMA
中科院分区：
文献类型：
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作者：
Shi, J;Shaw, CL;Mann, DMA
我们研究了连续70例临床诊断为额颞叶变性（FTLD）而死亡的患者大脑中痴呆的病理相关性。临床误诊率低，仅3例（4%）患者未显示符合此诊断的病理变化，1例患者为阿尔茨海默病，2例为脑血管病（CVD）。在其余67例患者中，最常见的潜在组织学原因是泛素病理学，其中24例（36%）受影响。在这些中，泛素阳性包涵体存在于大脑皮层中的小，圆形或新月形结构内的细胞质的第二层的神经元，连同卷曲或曲线体内的神经突，并在海马中的齿状回颗粒细胞的细胞质内的小，固体和更球形的包涵体。在一个病人，“猫眼”或“豆状”核内泛素包涵体也存在。第二种最常见的组织学类型是缺乏独特组织学的痴呆（DLDH），其中既不存在tau蛋白也不存在泛素包涵体，有16例（24%）受到影响。在14例（21%）病例中观察到Pick型组织学，在11例（16%）病例中存在与17号染色体（FTDP-17）相关的额颞叶痴呆（FTD）相关的tau组织学变化。1例（1%）显示异常tau病理学，无法分配给任何其他tau组。仅1例（1%）出现神经元中间丝包涵体痴呆。没有出现在包涵体肌病伴骨佩吉特病和额颞叶痴呆中所见的泛素化、含valosin蛋白免疫反应性核内包涵体的病例。临床病理学相关性表明，这些组织学亚型中的任何一种均可与FTD相关。然而，对于FTD伴运动神经元疾病（FTD+MND）、语义性痴呆或原发性进行性失语（PA），组织学特征为泛素型或DLDH型;仅在1例PA病例中观察到Pick型组织学。后三种临床亚型均与tau基因突变和FTDP-17型tau病理学无关。所有进行性失用症病例均与Pick型组织学相关。因此，现有数据表明，尽管泛素病理学是与FTLD相关的最常见组织学形式，但该病理学与该疾病的任何特定临床形式（包括FTD+MND）没有紧密联系，也不是该疾病的病理学诊断。
We have investigated the pathological correlates of dementia in the brains from a consecutive series of 70 patients dying with a clinical diagnosis of frontotemporal lobar degeneration (FTLD). Clinical misdiagnosis rate was low with only 3 patients (4%) failing to show pathological changes consistent with this diagnosis; 1 patient had Alzheimer's disease and 2 had cerebrovascular disease (CVD). In the remaining 67 patients, the most common underlying histological cause was ubiquitin pathology with 24 (36%) cases so affected. In these, ubiquitin-positive inclusions were present in the cerebral cortex as small, rounded or crescent-shaped structures within the cytoplasm of neurones of layer II, together with coiled or curvilinear bodies within neurites, and in the hippocampus as small, solid and more spherical-shaped inclusion bodies within the cytoplasm of dentate gyrus granule cells. In one patient, "cat's eye" or "lentiform" intranuclear ubiquitin inclusions were also present. The second most common histological type was dementia lacking distinctive histology (DLDH), in which neither tau nor ubiquitin inclusions were present, with 16 cases (24%) being affected. Pick-type histology was seen in 14 cases (21%) and tau histological changes associated with frontotemporal dementia (FTD) linked to chromosome 17 (FTDP-17) were present in 11 cases (16%). One case (1%) showed an unusual tau pathology that could not be allocated to any of the other tau groups. Only 1 case (1%) had neuronal intermediate filament inclusion dementia. No cases with ubiquitinated, valosin-containing protein-immunoreactive intranuclear inclusion bodies of the type seen in inclusion body myopathy with Paget's disease of bone and frontotemporal dementia were seen. Clinicopathological correlation showed that any of these histological subtypes can be associated with FTD. However, for FTD with motor neurone disease (FTD+MND), semantic dementia or primary progressive aphasia (PA), the histological profile was either ubiquitin type or DLDH type; Pick-type histology was seen in only 1 case of PA. None of these latter three clinical subtypes was associated with a mutation in tau gene and FTDP-17 type of tau pathology. All cases of progressive apraxia were associated with Pick-type histology. Present data therefore indicate that, although ubiquitin pathology is the most common histological form associated with FTLD, this pathology is not tightly linked with, nor is pathologically diagnostic for, any particular clinical form of the disease, including FTD+MND.