Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), atypical parkinsonisms, frontotemporal dementia (FTLD) and prion diseases are characterized by the accumulation of misfolded proteins in the central nervous system (CNS). Although the cause for the initiation of protein aggregation is not well understood, these aggregates are disease-specific. For instance, AD is characterized by the intraneuronal accumulation of tau and extracellular deposition of amyloid-β (Aβ), PD is marked by the intraneuronal accumulation of α-synuclein, many FTLD are associated with the accumulation of TDP-43 while prion diseases show aggregates of misfolded prion protein. Hence, misfolded proteins are considered disease-specific biomarkers and their identification and localization in the CNS, collected postmortem, is required for a definitive diagnosis. With the development of two innovative cell-free amplification techniques named Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking-Induced Conversion (RT-QuIC), traces of disease-specific biomarkers were found in CSF and other peripheral tissues (e.g., urine, blood, and olfactory mucosa) of patients with different NDs. These techniques exploit an important feature shared by many misfolded proteins, that is their ability to interact with their normally folded counterparts and force them to undergo similar structural rearrangements. Essentially, RT-QuIC and PMCA mimic in vitro the same pathological processes of protein misfolding which occur in vivo in a very rapid manner. For this reason, they have been employed for studying different aspects of protein misfolding but, overall, they seem to be very promising for the premortem diagnosis of NDs.

诸如阿尔茨海默氏病（AD），帕金森氏病（PD），非典型帕金森氏病，额颞痴呆（FTLD）和病毒病等神经退行性疾病（NDs）的特征在于中枢神经系统（CNS）中错误折叠的蛋白质积累。尽管尚未很好地了解引发蛋白质聚集的原因，但这些聚集体是疾病特异性的。例如，AD的特征是tau在神经元内积聚，淀粉样β（Aβ）在细胞外沉积，PD的特征在于α-突触核蛋白在神经元内积聚，许多FTLD与TDP-43的积聚有关，而病毒疾病显示折叠的病毒蛋白的聚集体。因此，错误折叠的蛋白质被认为是疾病特异性的生物标志物，它们在中枢神经系统中的鉴定和定位被收集验尸是确定诊断所必需的。随着两种创新的无细胞扩增技术的发展，即蛋白错误折叠循环扩增（PMCA）和实时Quaking诱导转化（RT-QuIC），在CSF和其他周围组织（例如，不同ND患者的尿液，血液和嗅觉粘膜）。这些技术利用了许多错误折叠的蛋白质共有的重要特征，即它们与正常折叠的对应物相互作用并迫使它们进行相似的结构重排的能力。本质上，RT-QuIC和PMCA在体外模拟了体内发生的蛋白质错误折叠的相同病理过程以非常迅速的方式 因此，它们已被用于研究蛋白质错折叠的不同方面，但是总的来说，它们似乎对NDs的死前诊断非常有前途。