Shi Jing, Shaw Catherine L, Du Plessis Daniel, Richardson Anna M T, Bailey Kathryn L, Julien Camille, Stopford Cheryl, Thompson Jennifer, Varma Anoop, Craufurd David, Tian Jinzhou, Pickering-Brown Stuart, Neary David, Snowden Julie S, Mann David M A
Clinical Neuroscience Research Group, University of Manchester, Greater Manchester Neurosciences Centre, Hope Hospital, Stott Lane, Salford M6 8HD, UK.
Acta Neuropathol. 2005 Nov;110(5):501-12. doi: 10.1007/s00401-005-1079-4. Epub 2005 Oct 13.
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.
我们对70例临床诊断为额颞叶变性（FTLD）并死亡患者的大脑进行研究，以探寻痴呆的病理相关因素。临床误诊率较低，仅有3例（4%）未表现出与该诊断相符的病理变化；1例患有阿尔茨海默病，2例患有脑血管疾病（CVD）。在其余67例患者中，最常见的潜在组织学病因是泛素病理改变，有24例（36%）受此影响。在这些病例中，泛素阳性包涵体存在于大脑皮质，表现为II层神经元胞质内的小圆形或新月形结构，以及神经突内的卷曲或曲线形小体；在海马体中，表现为齿状回颗粒细胞胞质内的小的、实心的、更呈球形的包涵体。在1例患者中，还存在“猫眼”或“透镜状”核内泛素包涵体。第二常见的组织学类型是缺乏特征性组织学改变的痴呆（DLDH），其中既没有tau包涵体也没有泛素包涵体，有16例（24%）受此影响。14例（21%）可见Pick型组织学改变，11例（16%）存在与17号染色体连锁的额颞叶痴呆（FTD）相关的tau组织学改变（FTDP - 17）。1例（1%）表现出一种不寻常的tau病理改变，无法归入其他任何tau组。仅有1例（1%）患有神经元中间丝包涵体痴呆。未见到在骨Paget病合并包涵体肌病及额颞叶痴呆中所见的那种泛素化、含缬酪肽蛋白免疫反应性核内包涵体病例。临床病理相关性分析表明，这些组织学亚型中的任何一种都可能与FTD相关。然而，对于合并运动神经元病的FTD（FTD + MND）、语义性痴呆或原发性进行性失语（PA），组织学特征要么是泛素型要么是DLDH型；仅1例PA可见Pick型组织学改变。后三种临床亚型均未与tau基因突变及FTDP - 17型tau病理改变相关。所有进行性失用症病例均与Pick型组织学改变相关。因此，目前的数据表明，尽管泛素病理改变是与FTLD相关的最常见组织学形式，但这种病理改变与该疾病的任何特定临床形式，包括FTD + MND，并无紧密联系，也不具有病理诊断意义。
