Tissue accumulation of abnormal aggregates of amyloidogenic proteins such as prion protein, α-synuclein, and tau represents the hallmark of most common neurodegenerative disorders and precedes the onset of symptoms by years. As a consequence, the sensitive and specific detection of abnormal forms of these proteins in patients’ accessible tissues or fluids as biomarkers may have a significant impact on the clinical diagnosis of these disorders. By exploiting seeded polymerization propagation mechanisms to obtain cell-free reactions that allow highly amplified detection of these amyloid proteins, novel emerging in vitro techniques, such as the real-time quaking-induced conversion assay (RT-QuIC) have paved the way towards this important goal. Given its high accuracy in identifying misfolded forms of prion protein from Creutzfeldt-Jakob disease (CJD) CSF, RT-QuIC has already been included in the diagnostic criteria for the clinical diagnosis of sporadic CJD, the most common human prion disease. By showing that this assay may also accurately discriminate between Lewy body disorders and other forms of parkinsonisms or dementias, more recent studies strongly suggested that CSF RT-QuIC can also be successfully applied to synucleinopathies. Finally, preliminary encouraging data also suggested that CSF RT-QuIC might also work for tau protein, and accurately distinguish between 3R- and 4R tauopathies, including Pick’s disease, progressive supranuclear palsy, and corticobasal degeneration. Here we will review the state of the art of cell-free aggregation assays, their current diagnostic value and putative limitations, and the future perspectives for their expanded use in clinical practice.

中文翻译：

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致力于改善神经退行性疾病的早期诊断：蛋白质淀粉样蛋白体外转化测定的新兴作用。

淀粉样蛋白原蛋白（例如病毒蛋白，α-突触核蛋白和tau蛋白）的异常聚集体的组织蓄积代表了最常见的神经退行性疾病的标志，并且在症状发作之前已经多年。结果，敏感且特异性地检测患者可及组织或体液中这些蛋白质异常形式的生物标志物可能对这些疾病的临床诊断产生重大影响。通过利用种子聚合传播机制来获得无细胞反应，从而可以高度扩增地检测这些淀粉样蛋白，新出现的体外技术，例如实时地震诱导的转化测定法（RT-QuIC），为实现这一目标铺平了道路。重要目标。鉴于RT-QuIC能够高度准确地识别出来自Creutzfeldt-Jakob病（CJD）CSF的病毒蛋白的错误折叠形式，因此它已被纳入散发性CJD（最常见的人类pr病毒病）的临床诊断标准中。通过证明该测定方法还可以准确地区分路易氏体病和其他形式的帕金森氏症或痴呆症，最近的研究强烈表明，CSF RT-QuIC也可以成功应用于突触核蛋白病。最后，初步的令人鼓舞的数据还表明，CSF RT-QuIC也可能适用于tau蛋白，并能准确地区分3R-和4R tauopathies，包括Pick's病，进行性核上性麻痹和皮质基底变性。在这里，我们将回顾无细胞聚集测定的最新技术，