Table 1.

List of studies performed using Real Time-Quaking Induced Conversion (RT-QuIC) in cerebrospinal fluid (CSF) from patients affected by different prion diseases. A summary of the most relevant parameters such as RT-QuIC substrate, assay sensitivity, and specificity are included. Creutzfeldt-Jakob disease (CJD), Sporadic Creutzfeldt-Jakob disease (sCJD), iatrogenic Creutzfeldt-Jakob disease (iCJD), prion protein (PrP), cerebrospinal fluid (CSF), Gerstmann-Sträussler-Scheinker syndrome (GSS), genetic Creutzfeldt-Jakob disease (gCJD), Familial Fatal Insomnia (FFI), Amyotrophic Lateral Sclerosis (ALS), Variably protease-sensitive prionopathy (VPSPr).

Prion Diseases	RT-QuIC Substrate	Sensitivity	Specificity	Observations	Reference
sCJD iCJD	Full-length recombinant human 129M PrP	>80%	100%	Just two iCJD cases. Controls included other neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease, etc.) All samples correspond to post-mortem collected CSF.	Atarashi et al. 2011 [92]
sCJD	Full-length recombinant Syrian hamster PrP	89%	99%	Controls included patients suspected of sCJD but finally diagnosed with other neurodegenerative disorders. All samples correspond to post-mortem collected CSF.	McGuire et al. 2012 [94]
GSS (P102L) gCJD (E200K, V203I) FFI	Full-length recombinant human 129M PrP	GSS 89% gCJD (E200K) 81.8% gCJD (V203I) 100% FFI 83.3%	100%	14-3-3 and tau analysis of the GSS and FFI samples detected only 20% and 8.3% of the positive cases, respectively.	Sano et al. 2013 [95]
sCJD gCJD	Full-length recombinant Syrian hamster PrP	70%	100%	CSF samples were obtained from patients with possible or probable CJD (alive) and with other neurologic disorders (Alzheimer’s disease, Parkinson’s disease, etc.)	Orrú et al. 2014 [96]
sCJD	Truncated recombinant Syrian hamster PrP (90–231)	96%	100%	CSF samples were obtained from patients with possible or probable CJD at the time of sampling, as well as from the patients with other neurologic disorders, including Alzheimer’s disease, ALS, atypical Parkinsonism, etc.	Orrú et al. 2015 [97]
sCJD gCJD (E200K,V210I) FFI	Sheep-Syrian hamster chimeric recombinant PrP (Syrian hamster 14–128 followed by sheep residues 141 to 234)	85%	99%	Control group composed by patients with either clinically or pathologically defined alternative diagnosis (Alzheimer’s disease, Lewy body dementia, Parkinson’s disease, psychiatric disorders, etc.) Lumbar puncture in sCJD samples was done in early, middle, or late disease stage.	Cramm et al. 2015 and 2016 [98,99]
sCJD	Full-length recombinant human 129M PrP	76.5%	100%	Negative control with artificial CSF.	Park et al. 2016 [100]
sCJD gCJD (E200K and V210I) GSS (P102L)	Truncated recombinant Syrian hamster PrP (90–231)	94%	100%	Controls included patients with other neurodegenerative diseases (multiple sclerosis, Alzheimer’s disease, etc.).	Groveman et al. 2017 [101]
sCJD VPSPr gCJD	Full-length recombinant Syrian hamster PrP	sCJD 75.9–82.7% VPSPr 0% gCJD 91.3%	99.4%	Two hundred and twenty-seven, 97, and 29 samples of definite, probable, and possible sCJD were analyzed; 348 cases of non-CJD patients were used as negative controls. Along with these, 1 case of VPSPr and 46 cases of gCJD were also tested.	Lattanzio et al. 2017 [72]
sCJD gCJD (E200K, V210I and V180I) GSS (P102L)	Truncated recombinant Syrian hamster PrP (90–231)	sCJD 95% gCJD 75%	100%	All non–prion disease control CSF samples, including those originally with suspected prion disease, were negative. The single case of gCJD with V180I mutation was always negative. Probable, possible, and suspected cases were included, being diagnosis confirmed in all cases post-mortem.	Bongianni et al. 2017 [102]
sCJD gCJD (E200K and V210I) FFI GSS (A117V, P102L)	Truncated Recombinant Syrian Hamster PrP (90–231)	95%	98.5%	Specificity is reduced due to a repeatedly positive Lewy Body Dementia case that may have also had a subclinical prion disease. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1.	Foutz et al. 2017 [103]
sCJD gCJD (E200K and V210I) GSS (P102L) VPSPr	Truncated recombinant Syrian hamster PrP (90–231)	sCJD ranging from 90% to 100% depending on the subtype gCJD 100% GSS 25% VPSPr 100%	100%	CSF Analysis of 339 patients: 166 definite CJD 73 probable CJD 100 negative CJD	Franceschini et al. 2017 [104]
sCJD	Truncated recombinant Syrian hamster PrP (90–231)	96%	100%	Control cases included patients diagnosed by many other neurodegenerative disorders including Alzheimer’s disease, Lewy body dementia, Parkinson’s disease, etc.	Fiorini et al. 2020 [105]