Parobkova Eva, van der Zee Julie, Dillen Lubina, Van Broeckhoven Christine, Rusina Robert, Matej Radoslav
Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia.
National Reference Laboratory for Human Prion Diseases, Thomayer Hospital, Prague, Czechia.
Front Neurol. 2020 Nov 30;11:596108. doi: 10.3389/fneur.2020.596108. eCollection 2020.
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common type of a group of transmissible spongiform encephalopathies (prion diseases). The etiology of the sporadic form of CJD is still unclear. sCJD can occur in combination with other neurodegenerative diseases, which further complicates the diagnosis. Alzheimer's disease (AD), e.g., is often seen in conjunction with sCJD. In this study, we performed a systematic analysis of 15 genes related to the most important neurodegenerative diseases - AD, frontotemporal dementia, amyotrophic lateral sclerosis, prion disease, and Parkinson's disease - in a cohort of sCJD and sCJD in comorbidity with AD and primary age-related proteinopathy (PART). A total of 30 neuropathologically verified cases of sCJD with and without additional proteinopathies were included in the study. In addition, we compared microtubule-associated protein tau haplotypes between sCJD patients and patients with sCJD and PART or sCJD and AD. Then we studied the interaction between the Apolipoprotein E gene ( and in sCJD patients. We did not find any causal mutations in the neurodegenerative disease genes. We did detect a p.E318G missense variant of uncertain significance (VUS) in in three patients. In , we also found a previously described non-pathogenic insertion (p.P84_Q91Q). Our pilot study failed to find any critical differences between pure sCJD and sCJD in conjunction with other comorbid neurodegenerative diseases. Further investigations are needed to better understand this phenomenon.
散发性克雅氏病（sCJD）是一组可传播性海绵状脑病（朊病毒病）中最常见的类型。散发性克雅氏病的病因仍不清楚。sCJD可与其他神经退行性疾病并发，这使得诊断更加复杂。例如，阿尔茨海默病（AD）常与sCJD同时出现。在本研究中，我们对15个与最重要的神经退行性疾病——AD、额颞叶痴呆、肌萎缩侧索硬化症、朊病毒病和帕金森病相关的基因进行了系统分析，研究对象为一组sCJD患者以及合并AD和原发性年龄相关性蛋白病（PART）的sCJD患者。该研究共纳入了30例经神经病理学证实的有无其他蛋白病的sCJD病例。此外，我们比较了sCJD患者与合并PART或AD的sCJD患者之间的微管相关蛋白tau单倍型。然后我们研究了载脂蛋白E基因（ ）在sCJD患者中的相互作用。我们在神经退行性疾病基因中未发现任何致病突变。我们在3例患者中检测到 基因的一个意义未明的错义变异（VUS）p.E318G。在 中，我们还发现了一个先前描述的非致病性插入（p.P84_Q91Q）。我们的初步研究未能发现单纯sCJD与合并其他神经退行性疾病的sCJD之间存在任何关键差异。需要进一步研究以更好地理解这一现象。
