Department of Neurology, Second Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, China.
Department of Anesthesiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, China.
Exp Gerontol. 2024 Mar;187:112366. doi: 10.1016/j.exger.2024.112366. Epub 2024 Feb 6.
synucleinopathies are diseases characterized by the aggregation of α-synuclein (α-syn), which forms fibrils through misfolding and accumulates in a prion-like manner. To detect the presence of these α-syn aggregates in clinical samples, seed amplification assays (SAAs) have been developed. These SAAs are capable of amplifying the α-syn seeds, allowing for their detection. αSyn-SAAs have been reported under the names 'protein misfolding cyclic amplification' (αSyn-PMCA) and 'real-time quaking-induced conversion'α-Syn-RT-QuIC. The α-Syn RT-QuIC, in particular, has been adapted to amplify and detect α-syn aggregates in various biospecimens, including cerebrospinal fluid (CSF), skin, nasal brushing, serum and saliva. The α-syn RT-QuIC assay has demonstrated good sensitivity and specificity in detecting pathological α-syn, particularly in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) cases, with an accuracy rate of up to 80 %. Additionally, differential diagnosis between DLB and PD, as well as PD and multiple system atrophy (MSA), can be achieved by utilizing certain kinetic thioflavin T (ThT) parameters and other parameters. Moreover, the positive detection of α-syn in the prodromal stage of synucleinopathies provides an opportunity for early intervention and management. In summary, the development of the α-syn RT-QuIC assay has greatly contributed to the field of synucleinopathies. Therefore, we review the development of α-syn RT-QuIC assay and describe in detail the recent advancements of α-syn RT-QuIC assay for detecting pathological α-syn in synucleinopathies.
突触核蛋白病是以α-突触核蛋白（α-syn）聚集为特征的疾病，α-syn 通过错误折叠形成纤维，并以类朊病毒样方式积累。为了在临床样本中检测这些α-syn 聚集物，已经开发了种子扩增测定法（SAAs）。这些 SAA 能够扩增α-syn 种子，从而进行检测。αSyn-SAA 有“蛋白质错误折叠循环扩增”（αSyn-PMCA）和“实时震颤诱导转换”α-Syn-RT-QuIC 两种叫法。特别是α-Syn RT-QuIC 已经适应于扩增和检测各种生物样本中的α-syn 聚集物，包括脑脊液（CSF）、皮肤、鼻刷、血清和唾液。α-syn RT-QuIC 测定法在检测病理性α-syn 方面表现出良好的灵敏度和特异性，特别是在帕金森病（PD）和路易体痴呆（DLB）病例中，准确率高达 80%。此外，通过利用某些硫黄素 T（ThT）动力学参数和其他参数，可以实现 DLB 与 PD 以及 PD 与多系统萎缩（MSA）之间的鉴别诊断。此外，在突触核蛋白病的前驱期阳性检测到α-syn 为早期干预和管理提供了机会。总之，α-syn RT-QuIC 测定法的发展为突触核蛋白病领域做出了巨大贡献。因此，我们综述了α-syn RT-QuIC 测定法的发展，并详细描述了该方法在检测突触核蛋白病中病理性α-syn 方面的最新进展。
