额颞叶变性tau 蛋白包涵体病的海马神经病理学：BrainNet Europe 联合会的一项研究。

Neuropathology of the hippocampus in FTLD-Tau with Pick bodies: a study of the BrainNet Europe Consortium.

机构信息

Institute of Neurology, Medical University of Vienna, Austria,Semmelweis University Neuropathology and Prion Disease Reference Center (Former Department of Neuropathology, National Institute of Psychiatry and Neurology), Budapest, Hungary,Netherlands Brain Bank and VU University Medical Center, Amsterdam,Erasmus MC, Rotterdam, The Netherlands,Clinical Neuropathology Department, King's College Hospital,King's College London, MRC Centre for Neurodegeneration Research, Department of Clinical Neuroscience, Institute of Psychiatry, London,Department of Neuropathology, John Radcliffe Hospital, Oxford,Department of Pathology, University of Edinburgh, Western General Hospital, Edinburgh, UK,Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy,Institut de Neuropatologia, Hospital Universitari de Bellvitge, Universitat de Bacelona, Hospitalet de Llobregat, Barcelona, Spain,Centre for Neuropathology and Prion Research, Ludwig-Maximilians-University, and Neurobiobank Munich/BrainNet Germany, Munich, Germany,Department of Geriatrics, Karolinska Institutet, HuddingeRudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Neuroscience and Neurology, Kuopio University, Kuopio, Finland.

出版信息

Neuropathol Appl Neurobiol. 2013 Feb;39(2):166-78. doi: 10.1111/j.1365-2990.2012.01272.x.

DOI:10.1111/j.1365-2990.2012.01272.x

PMID:22471883

Abstract

AIMS

Frontotemporal lobar degeneration with Pick bodies (Pick's disease) is characterized by the presence of tau immunoreactive spherical structures in the cytoplasm of neurones. In view of confusion about the molecular pathology of Pick's disease, we aimed to evaluate the spectrum of tau pathology and concomitant neurodegeneration-associated protein depositions in the characteristically affected hippocampus.

METHODS

We evaluated immunoreactivity (IR) for tau (AT8, 3R, 4R), α-synuclein, TDP43, p62, and ubiquitin in the hippocampus, entorhinal and temporal cortex in 66 archival cases diagnosed neuropathologically as Pick's disease.

RESULTS

Mean age at death was 68.2 years (range 49-96). Fifty-two (79%) brains showed 3R immunoreactive spherical inclusions in the granule cells of the dentate gyrus. These typical cases presented mainly with the behavioural variant of frontotemporal dementia, followed by progressive aphasia, mixed syndromes or early memory disturbance. α-Synuclein IR was seen only in occasional spherical tau-positive inclusions, TDP-43 IR was absent, and 4R IR was present only as neurofibrillary tangles in pyramidal neurones. Aβ IR was observed in 16 cases; however, the overall level of Alzheimer's disease-related alterations was mainly low or intermediate (n = 3). Furthermore, we identified six cases with unclassifiable tauopathy.

CONCLUSIONS

(i) Pick's disease may occur also in elderly patients and is characterized by a relatively uniform pathology with 3R tau inclusions particularly in the granule cells of dentate gyrus; (ii) even minor deviation from these morphological criteria suggests a different disorder; and (iii) immunohistological revision of archival cases expands the spectrum of tauopathies that require further classification.

摘要

目的

额颞叶变性伴 Pick 小体（Pick 病）的特征是神经元细胞质中存在 tau 免疫反应性球形结构。鉴于对 Pick 病的分子病理学存在混淆，我们旨在评估特征性受累海马区 tau 病理学及伴随的神经退行性相关蛋白沉积谱。

方法

我们评估了 66 例经神经病理学诊断为 Pick 病的存档病例中海马、内嗅皮质和颞叶皮质中 tau（AT8、3R、4R）、α-突触核蛋白、TDP43、p62 和泛素的免疫反应性（IR）。

结果

死亡时的平均年龄为 68.2 岁（范围 49-96 岁）。52 例（79%）脑显示齿状回颗粒细胞中存在 3R 免疫反应性球形包涵体。这些典型病例主要表现为额颞叶痴呆的行为变异型，其次为进行性失语、混合综合征或早期记忆障碍。偶尔可见 α-突触核蛋白 IR 阳性的球形 tau 阳性包涵体，TDP-43 IR 缺失，4R IR 仅在锥体神经元中呈神经纤维缠结。16 例观察到 Aβ IR；然而，阿尔茨海默病相关改变的总体水平主要为低或中（n=3）。此外，我们鉴定了 6 例无法分类的 tau 病。