Ascari Lucas M, Rocha Stephanie C, Gonçalves Priscila B, Vieira Tuane C R G, Cordeiro Yraima
Faculty of Pharmacy, Pharmaceutical Biotechnology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Front Bioeng Biotechnol. 2020 Oct 20;8:585896. doi: 10.3389/fbioe.2020.585896. eCollection 2020.
Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, arise from the structural conversion of the monomeric, cellular prion protein (PrP) into its multimeric scrapie form (PrP). These pathologies comprise a group of intractable, rapidly evolving neurodegenerative diseases. Currently, a definitive diagnosis of TSE relies on the detection of PrP and/or the identification of pathognomonic histological features in brain tissue samples, which are usually obtained postmortem or, in rare cases, by brain biopsy (antemortem). Over the past two decades, several paraclinical tests for antemortem diagnosis have been developed to preclude the need for brain samples. Some of these alternative methods have been validated and can provide a probable diagnosis when combined with clinical evaluation. Paraclinical tests include cell-free conversion techniques, such as the real-time quaking-induced conversion (RT-QuIC), as well as immunoassays, electroencephalography (EEG), and brain bioimaging methods, such as magnetic resonance imaging (MRI), whose importance has increased over the years. PrP is the main biomarker in TSEs, and the RT-QuIC assay stands out for its ability to detect PrP in cerebrospinal fluid (CSF), olfactory mucosa, and dermatome skin samples with high sensitivity and specificity. Other biochemical biomarkers are the proteins 14-3-3, tau, neuron-specific enolase (NSE), astroglial protein S100B, α-synuclein, and neurofilament light chain protein (NFL), but they are not specific for TSEs. This paper reviews the techniques employed for definite diagnosis, as well as the clinical and paraclinical methods for possible and probable diagnosis, both those in use currently and those no longer employed. We also discuss current criteria, challenges, and perspectives for TSE diagnosis. An early and accurate diagnosis may allow earlier implementation of strategies to delay or stop disease progression.
传染性海绵状脑病（TSEs），也称为朊病毒病，是由单体细胞朊蛋白（PrP）向其多聚体瘙痒病形式（PrP）的结构转变引起的。这些病症包括一组难治性、快速进展的神经退行性疾病。目前，TSE的确诊依赖于检测PrP和/或识别脑组织样本中的特征性组织学特征，这些样本通常在死后获取，或在罕见情况下通过脑活检（生前）获取。在过去二十年中，已经开发了几种用于生前诊断的临床旁检查，以避免需要脑样本。其中一些替代方法已经得到验证，并且与临床评估相结合时可以提供可能的诊断。临床旁检查包括无细胞转化技术，如实时震颤诱导转化（RT-QuIC），以及免疫测定、脑电图（EEG）和脑生物成像方法，如磁共振成像（MRI），其重要性多年来一直在增加。PrP是TSEs中的主要生物标志物，RT-QuIC检测因其能够高灵敏度和特异性地检测脑脊液（CSF）、嗅觉粘膜和皮节皮肤样本中的PrP而脱颖而出。其他生化生物标志物是蛋白质14-3-3、tau、神经元特异性烯醇化酶（NSE）、星形胶质细胞蛋白S100B、α-突触核蛋白和神经丝轻链蛋白（NFL），但它们并非TSEs所特有。本文回顾了用于明确诊断的技术，以及用于可能和疑似诊断的临床和临床旁方法，包括目前使用的和不再使用的方法。我们还讨论了TSE诊断的当前标准、挑战和前景。早期准确的诊断可能有助于更早地实施延缓或阻止疾病进展的策略。
