Table 4.
CSF RT-QuIC protocols and diagnostic accuracy in synucleinopathies
| 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% |
Diagnostic groups/cohorts are meant to be clinically defined as probable cases, unless otherwise specified. Sensitivities values for diagnostic groups ≤5 are not included
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
aA preliminary not peer-reviewed draft of this study has been posted as preprint