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Table 4 CSF RT-QuIC protocols and diagnostic accuracy in synucleinopathies

From: Towards an improved early diagnosis of neurodegenerative diseases: the emerging role of in vitro conversion assays for protein amyloids

Syn substrate Reaction buffer Parameters Cohort size (N) Sens. Spec. Ref.
WT Hu (commercial) 0,1 g/L substrate, 15 μL seed, 100 mmol/L PB 37 zirconia/silica bead, 1 min double orbital shaking 200 rpm, 14 min rest, 30 °C cohort 1 (definite cases):    [27]
12 pure DLB 92%  
17 mixed DLB + AD 65%  
13 AD+incidental LB 15%  
20 ctrl, 30 AD   100%
cohort 2:   
20 PD 95%  
15 ctrl   100%
53 PD 84%   [89]
17 MSA 35%  
14 other synucleinopathies 86%  
26 non α-syn parkinsonism   89%
52 ctrl   98%
10 PD 90%   [32]
15 PD-LRRK2 40%  
16 LRRK2 carriers 19%  
10 ctrl   80%
105 PD 96%   [44]
79 ctrl   82%
52 iRBD 90%   [42]a
9 ctrl   78%
K23Q Hu (home-made) 0,1 g/L substrate, 15 μL seed, 0,0015% SDS 6 silica beads (0.8 mm diameter), 1 min double orbital shaking 400 rpm, 1 min rest, 42 °C 17 DLB 94%   [37]
12 PD 92%  
16 AD   100%
12 ctrl   100%
WT Hu (home-made) 0,1 g/L substrate, 15 μL seed, 100 mmol/L PB 37 zirconia/silica bead, 1 min double orbital shaking 200 rpm, 14 min rest, 30 °C cohort 1 (definite cases):    [12]
7/20 pure/mixed DLB, 1 MSA 93%  
49 ctrl   96%
cohort 2:   
20 DLB 85%  
6 poss DLB 0%  
10 AD   100%
0,1 g/L substrate, 15 μL seed, 0,0015% SDS 6 silica beads (0.8 mm diameter), 1 min double orbital shaking 400 rpm, 1 min rest, 42 °C 15 PD 100%   [52]
11 ctrl   100%
cohort 1 (definite cases):    [74]
21 LB-disorders 95%  
101 ctrl   98%
cohort 2:   
71 PD 94%  
34 DLB 97%  
28 PAF 93%  
18 iRBD 100%  
17 AD   84%
30 PSP/CBS   100%
31 MSA   93.5%
62 ctrl   98%
1 g/L substrate, 40 μL seed, 100 mM PIPES 1 min shaking 500 rpm, 29 min rest, 37 °C 76 PD 88.5%   [83]
10 DLB 100%  
10 MSA 80%  
83 ctrl   94%
94 PD 94%   [82]
75 MSA 85%  
56 ctrl   100%
  1. Diagnostic groups/cohorts are meant to be clinically defined as probable cases, unless otherwise specified. Sensitivities values for diagnostic groups ≤5 are not included
  2. Abbreviations: Hu Human, WT Wild type, LB Lewy bodies, DLB Dementia with LB, AD Alzheimer’s disease, PD Parkinson’s disease, MSA Multiple system atrophy, iRBD Isolate REM sleep behavior disorder, PSP Progressive supranuclear palsy, CBS Corticobasal syndrome, PAF Pure autonomic failure, prob Probable, poss Possible, ctrl Controls
  3. aA preliminary not peer-reviewed draft of this study has been posted as preprint