Pathological α-synuclein detected by real-time quaking-induced conversion in synucleinopathies

• Published in: Experimental gerontology 2024-03, Vol.187, p.112366-112366, Article 112366
• Main Authors: Huang, Juan, Yuan, Xingxing, Chen, Lin, Hu, Binbin, Wang, Hui, Wang, Ye, Huang, Wei
• Format: Article
• Language: English
• Subjects: Aggregated α-synuclein; alpha-Synuclein; Humans; Parkinson Disease - diagnosis; Seed amplification assays; Self-propagation; Synucleinopathies; Synucleinopathies - diagnosis; Synucleinopathies - pathology; α-Syn RT-QuIC
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2024.112366

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. •Real-time quaking-induced conversion (RT-QuIC) has been adapted to amplify and detect α-syn aggregates in various biospecimens.•α-syn RT-QuIC has shown high sensitivity and specificity in diagnosising α-synucleinopathies.•α-syn RT-QuIC helps identifying individuals in the prodromal stage of α-synucleinopathies.