Distribution patterns of tau pathology in progressive supranuclear palsy
Distribution patterns of tau pathology in progressive supranuclear palsy
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DOI：
10.1007/s00401-020-02158-2
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发表时间：
2020-05-07
影响因子：
12.7
通讯作者：
Hoeglinger, Guenter U.
中科院分区：
文献类型：
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作者：
Kovacs, Gabor G.;Lukic, Milica Jecmenica;Hoeglinger, Guenter U.
进行性核上麻痹（PSP）是一种4R-Tauopathy，在神经元，星形胶质细胞和少突胶质细胞中占主导地皮层病理学，与各种临床表型相关。在本国际研究中，我们解决了一个问题，即在PSP病理学中是否可以识别顺序分布模式。我们评估了神经元，星形胶质细胞和寡头tau病理的热图和分布模式，及其在PSP的不同临床亚型中的组合中的术后大脑中的组合。我们使用条件概率和逻辑回归来模拟tau病理在不同大脑区域的顺序分布。 tau病理在不同临床亚型中均统一的pallido-Nigro-Luysian轴神经元中占主导地位。然而，临床亚型不仅通过总tau负载来区分，而且还通过细胞类型（神经元与神经胶质）特定脆弱性模式来区分大脑区域的特定脆弱性模式，表明tau病理的传播的独特动力学或电路特异性分离。对于理查森综合征（n = 81），我们通过细胞tau病理学的结合来识别大脑区域参与的六个顺序步骤。通过评估丘脑下核，帕利德斯球核，纹状体，小脑，带有齿状核以及牙齿核和枕皮层的评估，将其转化为实用神经病理学诊断的六个阶段。该系统可以通过强调它们表现出尾尾（小脑/齿状核）还是tho骨（皮质）（皮质）主要的或两种类型的模式来应用于进一步的临床亚型。定义TAU病理学的细胞特异性阶段有助于鉴定临床前或早期病例，以更好地理解早期病原事件，对理解疾病促进的临床亚型特异性动态具有影响，并为Tau-neuro-neuro-neuromimimimist insive tau-neuromimimist of Tau-neuromimist of分布模式。
Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains. We used conditional probability and logistic regression to model the sequential distribution of tau pathologies across different brain regions. Tau pathology uniformly predominates in the neurons of the pallido-nigro-luysian axis in different clinical subtypes. However, clinical subtypes are distinguished not only by total tau load but rather cell-type (neuronal versus glial) specific vulnerability patterns of brain regions suggesting distinct dynamics or circuit-specific segregation of propagation of tau pathologies. For Richardson syndrome (n = 81) we recognize six sequential steps of involvement of brain regions by the combination of cellular tau pathologies. This is translated to six stages for the practical neuropathological diagnosis by the evaluation of the subthalamic nucleus, globus pallidus, striatum, cerebellum with dentate nucleus, and frontal and occipital cortices. This system can be applied to further clinical subtypes by emphasizing whether they show caudal (cerebellum/dentate nucleus) or rostral (cortical) predominant, or both types of pattern. Defining cell-specific stages of tau pathology helps to identify preclinical or early-stage cases for the better understanding of early pathogenic events, has implications for understanding the clinical subtype-specific dynamics of disease-propagation, and informs tau-neuroimaging on distribution patterns.