Department of Neuropathology, Institute of Psychiatry and Neurology, Warsaw, Poland.
Department of Descriptive and Clinical Anatomy, Medical University of Warsaw, Warsaw, Poland.
J Neuropathol Exp Neurol. 2024 Mar 20;83(4):251-257. doi: 10.1093/jnen/nlae017.
Subacute sclerosing panencephalitis (SSPE) is a fatal, slowly progressive brain disorder caused by a mutated measles virus. Both subacute inflammatory and neurodegenerative mechanisms appear to play significant roles in the pathogenesis. TAR DNA-binding protein 43 (TDP-43) inclusions are a common co-pathology in several neurodegenerative disorders with diverse pathogenesis. In the present study, we examined brains of 16 autopsied SSPE patients for the presence of TDP-43 pathology and possible associations with tau pathology. Immunohistochemical staining identified TDP-43 inclusions in 31% of SSPE cases. TDP-43 pathology was widely distributed in the brains, most severely in the atrophied cerebral cortex (temporal and parietal), and most frequently as tangle- and thread-like neuronal cytoplasmic inclusions. It was associated with longer disease duration (>4 years) and tau pathology (all TDP-43-positive cases had tau-positive neurofibrillary tangles). This study demonstrates for the first time an association between TDP-43 pathology and SSPE. The co-occurrence of TDP-43 and tau aggregates and correlation with the disease duration suggest that both pathological proteins are involved in the neurodegenerative process induced by viral inflammation.
亚急性硬化性全脑炎（SSPE）是一种致命的、缓慢进展的脑疾病，由突变的麻疹病毒引起。亚急性炎症和神经退行性变机制似乎都在发病机制中起重要作用。TAR DNA 结合蛋白 43（TDP-43）包含体是几种具有不同发病机制的神经退行性疾病的常见伴随病理学。在本研究中，我们检查了 16 例尸检 SSPE 患者的大脑中是否存在 TDP-43 病理学，并可能与 tau 病理学相关。免疫组织化学染色在 31%的 SSPE 病例中发现了 TDP-43 包含体。TDP-43 病理学广泛分布于大脑中，在萎缩的大脑皮层（颞叶和顶叶）中最为严重，并且最常以缠结和线状神经元细胞质包含体的形式出现。它与疾病持续时间较长（>4 年）和 tau 病理学（所有 TDP-43 阳性病例均有 tau 阳性神经纤维缠结）有关。本研究首次证明了 TDP-43 病理学与 SSPE 之间存在关联。TDP-43 和 tau 聚集物的共存以及与疾病持续时间的相关性表明，这两种病理蛋白都参与了病毒炎症引起的神经退行性过程。
