Department of Neuropathology, Institute of Psychiatry and Neurology, Warsaw, Poland.
Department of Forensic Medicine, Medical University of Warsaw, Warsaw, Poland.
Folia Neuropathol. 2023;61(2):111-120. doi: 10.5114/fn.2023.128776.
Transactivation (TAR) DNA binding protein 43 kDa (TDP-43) inclusions frequently occur as a comorbid pathology in several neurodegenerative disorders, including Alzheimer's disease, Huntington's disease, Lewy body disease, and progressive supranuclear palsy, and may appear in association with nondegenerative neurological etiology, for example neoplastic, paraneoplastic, traumatic, or infectious. Relationships between various pathological proteins and mechanisms associated with TDP-43-induced neurodegeneration are still not fully understood. Thus, overlap of distinct neuropathological mechanisms frequently leads to greater brain atrophy and a more severe clinical course, suggesting the importance of co-pathologies in ante-mortem diagnosing and treatment. The present review aims to discuss the incidence, morphology, and role of TDP-43 pathology in the context of other dominant, hallmark pathologies, referred to as secondary TDP-43 proteinopathies. The previous part (Part 1) focused on common neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, and Lewy body disease, while the present part (Part 2) discusses TDP-43 pathology in rare neurodegenerative diseases and neurological diseases with nondegenerative etiology.
TDP-43 结合蛋白 43kDa（TDP-43）包含物经常作为几种神经退行性疾病（包括阿尔茨海默病、亨廷顿病、路易体病和进行性核上性麻痹）的合并病理学出现，并且可能与非变性神经病因相关联，例如肿瘤性、副肿瘤性、创伤性或感染性。各种病理蛋白之间的关系与 TDP-43 诱导的神经退行性变相关的机制仍不完全清楚。因此，不同神经病理学机制的重叠常常导致更大的脑萎缩和更严重的临床病程，这表明共病在生前诊断和治疗中的重要性。本综述旨在讨论 TDP-43 病理学在其他主要标志性病理学（称为次要 TDP-43 蛋白病）背景下的发生率、形态和作用。上一部分（第 1 部分）重点讨论了常见的神经退行性疾病，包括阿尔茨海默病、亨廷顿病和路易体病，而本部分（第 2 部分）讨论了罕见的神经退行性疾病和非变性病因的神经疾病中的 TDP-43 病理学。
