Abstract
The accumulation and deposition of α-synuclein aggregates in brain tissue is the main event in the pathogenesis of different neurodegenerative disorders grouped under the term of synucleinopathies. They include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. To date, the diagnosis of any of these disorders mainly relies on the recognition of clinical symptoms, when the neurodegeneration is already in an advanced phase. In the last years, several efforts have been carried out to develop new diagnostic tools for early diagnosis of synucleinopathies, with special interest to Parkinson's disease. The Protein-Misfolding Cyclic Amplification (PMCA) and the Real-Time Quaking-Induced Conversion (RT-QuIC) are ultrasensitive protein amplification assays for the detection of misfolded protein aggregates. Starting from the successful application in the diagnosis of human prion diseases, these techniques were recently tested for the detection of misfolded α-synuclein in brain homogenates and cerebrospinal fluid samples of patients affected by synucleinopathies. So far, only a few studies on a limited number of samples have been performed to test PMCA and RT-QuIC diagnostic reliability. Neverthless, these assays have shown very high sensitivity and specificity in detecting synucleinopathies even at the pre-clinical stage. Despite the application of PMCA and RT-QuIC for α-synuclein detection in biological fluids is very recent, these techniques seem to have the potential for identifying subjects that will be likely to develop synucleinopathies.
Highlights
Protein-Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking-Induced Conversion (RT-QuIC) represent two ultrasensitive protein amplification methods for detecting pathological protein aggregates in patients affected by protein misfolding disorders [1,2,3]
The aim of this review is to provide an overview on existing data on PMCA and RT-QuIC assays, and their possible application for the diagnosis of synucleinopathies
The first trials of PMCA on PrPSc date back to 2001 but only recently the αSyn-PMCA and RT-QuIC techniques have been applied for the amplification and detection of aggregates of misfolded α-syn
Summary
Protein-Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking-Induced Conversion (RT-QuIC) represent two ultrasensitive protein amplification methods for detecting pathological protein aggregates in patients affected by protein misfolding disorders [1,2,3]. Since α-synuclein (α-syn) follows aggregation mechanisms similar to PrP, PMCA and RT-QuIC assays were tested for the detection of misfolded α-syn in samples of patients affected by synucleinopathies [4,5,6,7,8,9]. Apart from the length of the lag-phase, Kang et al [82] suggested that differences in amyloid formation rate, ThT fluorescence maxima and integrated area under the curve show discrimination between seeded and unseeded samples, these features could be suitable for αSyn-PMCA and RT-QuIC data analysis.
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