额颞叶变性 TDP-43 免疫反应性病理亚型：临床和机制意义。
Frontotemporal Lobar Degeneration TDP-43-Immunoreactive Pathological Subtypes: Clinical and Mechanistic Significance.
机构信息
Department of Neuropathology, University of Tübingen, Tübingen, Germany.
DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
出版信息
Adv Exp Med Biol. 2021;1281:201-217. doi: 10.1007/978-3-030-51140-1_13.
Abstract
Frontotemporal lobar degeneration with TPD-43-immunoreactive pathology (FTLD-TDP) is subclassified based on the type and cortical laminar distribution of neuronal inclusions. The relevance of these pathological subtypes is supported by the presence of relatively specific clinical and genetic correlations. Recent evidence suggests that the different patterns of pathology are a reflection of biochemical differences in the pathological TDP-43 species, each of which is influenced by differing genetic factors. As a result, patient FTLD-TDP subtype may be an important factor to consider when developing biomarkers and targeted therapies for frontotemporal dementia. In this chapter, we first describe the pathological features, clinical and genetic correlations of the currently recognized FTLD-TDP subtypes. We then discuss a number of novel patterns of TDP-43 pathology. Finally, we provide an overview of what is currently known about the biochemical basis of the different FTLD-TDP subtypes and how this may explain the observed phenotypic and pathological heterogeneity.
摘要
额颞叶变性伴 TDP-43 免疫反应性病变（FTLD-TDP）根据神经元包涵体的类型和皮质层分布进行分类。这些病理亚型的相关性得到了相对特异性临床和遗传相关性的支持。最近的证据表明，不同的病理模式反映了病理 TDP-43 物种的生化差异，每种差异都受到不同遗传因素的影响。因此，患者 FTLD-TDP 亚型可能是开发针对额颞叶痴呆的生物标志物和靶向治疗方法时需要考虑的一个重要因素。在本章中，我们首先描述了目前公认的 FTLD-TDP 亚型的病理特征、临床和遗传相关性。然后，我们讨论了一些新型 TDP-43 病理模式。最后，我们概述了目前已知的不同 FTLD-TDP 亚型的生化基础以及这如何解释观察到的表型和病理异质性。
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