RT-QuIC for detection of prodromal α-synucleinopathies
2021; Elsevier BV; Volume: 20; Issue: 3 Linguagem: Inglês
10.1016/s1474-4422(21)00036-3
ISSN1474-4465
Autores Tópico(s)Alzheimer's disease research and treatments
ResumoThe concept of self-propagating proteins as a common causative feature in neurodegenerative diseases has led to the development of in-vitro misfolded protein amplification systems, such as protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC) assays. The RT-QuIC technique was first developed to detect abnormally folded prion protein (PrPSc) and is based on prion seed-induced misfolding and aggregation of recombinant protein substrate, accelerated by alternating cycles of shaking and rest in fluorescence plate readers (figure). The method is becoming increasingly important as a potential diagnostic tool in the field of neurodegenerative diseases. 1 Rossi M Candelise N Baiardi S et al. Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies. Acta Neuropathol. 2020; 140: 49-62 Crossref PubMed Scopus (36) Google Scholar , 2 Sano K Atarashi R Satoh K et al. Prion-like seeding of misfolded α-synuclein in the brains of dementia with Lewy body patients in RT-QuIC. Mol Neurobiol. 2018; 55: 3916-3930 PubMed Google Scholar , 3 Bongianni M Ladogana A Capaldi S et al. α-Synuclein RT-QuIC assay in cerebrospinal fluid of patients with dementia with Lewy bodies. Ann Clin Transl Neurol. 2019; 6: 2120-2126 Crossref PubMed Scopus (24) Google Scholar In The Lancet Neurology, Alex Iranzo and colleagues 4 Iranzo A Fairfoul G Chumbala Na Ayudhaya A et al. Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurol. 2021; 20: 203-212 Summary Full Text Full Text PDF PubMed Scopus (18) Google Scholar report the use of RT-QuIC to investigate α-synuclein in the CSF of patients with isolated rapid-eye-movement sleep behaviour disorder (IRBD), which can be part of the prodromal stage of α-synucleinopathies. Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational studyIn patients with IRBD, RT-QuIC detects misfolded α-synuclein in the CSF with both sensitivity and specificity of 90%, and α-synuclein positivity was associated with increased risk of subsequent diagnosis of Parkinson's disease or dementia with Lewy bodies. Detection of α-synuclein in the CSF represents a potential prodromal marker of Parkinson's disease and dementia with Lewy bodies. If these findings are replicated in additional cohorts, detection of CSF α-synuclein by RT-QuIC could be used to enrich IRBD cohorts in neuroprotective trials, particularly when assessing interventions that target α-synuclein. Full-Text PDF
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