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

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%	[44]
			52 iRBD	90%		[42]a
			9 ctrl		78%	[42]a
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%	[52]
			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^aA preliminary not peer-reviewed draft of this study has been posted as preprint

ISSN: 2051-5960