Acta Neuropathologica:进行性核上性麻痹中tau蛋白病理的分布模式

2020-07-20 MedSci原创 MedSci原创

进行性核上性麻痹(PSP)是一种4R-tau病理病,属于额颞叶变性(FTLD-tau)疾病

进行性核上性麻痹(PSP)是一种4R-tau病理。作者在本研究中,解决了进行性核上性麻痹病理学关于否可以识别顺序分布模式的问题。

作者评估了患者死后大脑中PSP的不同临床亚型中神经元,星形胶质和少突胶质tau病理及其组合的热图和分布模式。使用条件概率和逻辑回归来构建tau病理在不同大脑区域的顺序分布模型。在不同的临床亚型中,Tau病理在pallido-Nigro-luysian轴的神经元中始终占主要地位。然而,临床亚型不仅以总tau容量为特征,而且以脑区域的细胞类型(神经元与神经胶质)特异性易受性模式区分开,这表明tau病理学的传播具有独特的动力学。

对于理查森综合征(n = 81),我们认识到通过细胞tau病理学的结合,关联大脑区域的六个连续步骤。通过评估丘脑下核,苍白球,纹状体,具有齿状核的小脑以及额叶和枕叶皮质,这可分为六个阶段,用于实际的神经病理学诊断。 该系统可以通过强调其以尾部(小脑/齿状核)或尾部(皮层)为主,还是两种类型都适用于其他临床亚型。 定义tau病理的细胞特定阶段有助于识别临床前或早期病例,以更好地了解早期致病事件,对理解疾病传播的临床亚型特定动态具有影响,并为tau-神经影像学提供分布模式的信息。

方法:收集具有PSP病理学的不同临床亚型。病例根据PSP-RS,PSP-P,PSP-CBS,PSP-PGF,PSP-OM,PSP-PI,PSP-F或PSP-SL分组,采用可操作的运动障碍协会诊断性PSP标准。比较了tau细胞病理学的分布模式,并使用热图和条件概率矩阵来评估tau病理学的连续模式是否可以被识别以及临床亚型是否显示tau细胞病理学的独特分布模式。使用半定量评分(无,轻度,中度,无神经,轻度,中度,严重)。检查了以下解剖区域:中额额回,前扣带回,顶顶下回,颞上和中颞回,中央前回和枕叶皮质(包括横纹,副横纹和周纹区域),海马(锥体束层和齿状回)在一起),杏仁核,尾状丘脑,苍白球,丘脑和丘脑下核 ,中脑被膜,黑质,蓝斑,桥脑基底,被膜和以延髓为代表的下橄榄 用于条件概率分析),小脑白质(线和盘绕体)和齿状核(神经元和少有星形胶质头状病理)。对于包含丘脑底核和丘脑的区域,提供了丘脑底核的神经元tau病理评分,丘脑提供了星形胶质和少突胶质神经。

结果:神经元变性和tau病理的起始部位在临床亚型中似乎是相似的,但是动力学和传播方式将它们区分开。虽然神经元tau积累在发病机理中很重要,但星形胶质和少突胶质tau积累也很重要,并且可能先于纹状体,皮质区域,苍白球和小脑白质(与齿状核)的神经元tau病理有关。最后,作者提出了PSP-RS中的tau病理序列,该序列可识别病理模式并用于分期系统。看来这可能适用于各种PSP子类型。

原文链接:

Kovacs, G.G., Lukic, M.J., Irwin, D.J. et al. Distribution patterns of tau pathology in progressive supranuclear palsy. Acta Neuropathol 140, 99–119 (2020). https://doi.org/10.1007/s00401-020-02158-2

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