Tauopathy in human and experimental variant Creutzfeldt-Jakob disease
Tauopathy in human and experimental variant Creutzfeldt-Jakob disease
复制标题
DOI：
10.1016/j.neurobiolaging.2007.04.026
复制
发表时间：
2008-12-01
影响因子：
4.2
通讯作者：
Tagliavini, F.
中科院分区：
文献类型：
--
作者：
Giaccone, G.;Mangieri, M.;Tagliavini, F.
过度磷酸化tau（磷酸化tau）的脑积聚发生在包括阿尔茨海默病在内的几种神经退行性疾病中。在朊病毒疾病中，磷酸化tau蛋白沉积被描述为一种罕见的遗传形式，Gerstmann-Straussler-Scheinker病，但不被认为是Creutzfeldt-Jakob病神经病理学图像的一部分。本研究的目的是研究变异型克雅氏病（vCJD）患者的脑中是否存在与磷酸化tau蛋白积累相关的变化，该变异型克雅氏病与Gerstmann-Straussler-Scheinker病共享大量淀粉样蛋白形式的朊蛋白（PrP）沉积。分析扩展到vCJD的实验小鼠模型。我们检测到大量的磷酸化tau蛋白免疫反应性神经炎的配置文件，往往聚集在周围的PrP淀粉样蛋白沉积，不仅在大脑皮层，而且在小脑的所有vCJD患者检查，在A β的情况下。虽然不太经常，磷酸化tau定位在一些perikaria和树突。生化对应物是在大脑皮层的洗涤剂不溶性部分中存在磷酸化tau。在vCJD小鼠模型中，磷酸化tau蛋白免疫反应神经元的分布也与PrP沉积有关。这些发现表明与vCJD相关的PrP的异常形式触发tau蛋白病，并为与脑淀粉样变性相关的tau蛋白病理学的早期阶段提供了范例，包括阿尔茨海默病。(c)2007爱思唯尔公司All rights reserved.
Cerebral accumulation of hyperphosphorylated tau (phospho-tau) occurs in several neurodegenerative conditions including Alzheimer disease. In prion diseases, phospho-tau deposition has been described in a rare genetic form, Gerstmann-Straussler-Scheinker disease, but is not considered part of the neuropathological picture of Creutzfeldt-Jakob disease. Aim of this study was to investigate whether changes related to phospho-tau accumulation are present in the brain of patients with variant Creutzfeldt-Jakob disease (vCJD) that shares with Gerstmann-Straussler-Scheinker disease abundant prion protein (PrP) deposition in amyloid form. The analysis was extended to experimental mouse models of vCJD. We detected a large number of phospho-tau-immunoreactive neuritic profiles, often clustered around PrP amyloid deposits, not only in the cerebral cortex, but also in the cerebellum of all vCJD patients examined, in the absence of A beta. Although less constantly, phospho-tau was localized in some perikaria and dendrites. The biochemical counterpart was the presence of phospho-tau in the detergent-insoluble fraction of cerebral cortex. Phospho-tau-immunoreactive neuronal profiles were also found in association with PrP deposits in mouse models of vCJD. These findings suggest that the abnormal forms of PrP associated with vCJD trigger a tauopathy, and provide a paradigm for the early stages of tau pathology associated with cerebral amyloidoses, includes Alzheimer disease. (c) 2007 Elsevier Inc. All rights reserved.