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Table 2 Seeding activity of pathological α-syn in different samples from MSA patients measured by seeding aggregation assays

From: Multidimensional biomarkers for multiple system atrophy: an update and future directions

Sample

Research group

Participants

Assay(s)

Main findings

Cerebrospinal fluid

Singer et al. [46]

62 MSA, 16 PD, 13 DLB, 29 HC

PMCA

96.8% (60/62) of MSA patients showed positive seeding activity

Maximum ThT fluorescence significantly distinguished MSA from HC (AUC = 0.97) and PD/DLB (AUC = 0.93)

The fluorescence plateau occurred significantly earlier in MSA than PD/DLB

Shahnawaz et al. [45]

75 MSA, 94 PD, 56 HC

PMCA

86.7% (66/75) of MSA patients showed positive seeding activity

The fluorescence plateau occurred significantly earlier and was lower in MSA compared to PD

The biochemical and morphological features of α-syn aggregates were different between MSA and PD

Poggiolini et al. [47]

24 MSA, 74 PD, 45 iRBD, 55 HC

RT-QuIC

75.0% (18/24) of MSA patients showed positive seeding activity

RT-QuIC parameters were associated with UMSARS change

Rossi et al. [48]

33 MSA, 48 DLB, 60 AD, 31 PSP/CBS, 71 PD, 18 iRBD, 28 PAF, 143 HC

RT-QuIC

Pathologic seeding activity was seldom found in MSA

Quadalti et al. [49]

68 MSA, 116 PD, 52 PSP, 34 HC

RT-QuIC

Only 4.4% (3/68) of MSA patients showed positive seeding activity

Saliva

Luan et al. [50]

18 MSA, 75 PD, 36HC

RT-QuIC

61.1% (11/18) of MSA patients showed positive seeding activity

The fluorescence plateau significantly distinguished MSA from HC (AUC = 0.8194)

The lag phase was significantly longer in MSA than in PD

Skin

Wang et al. [41]

3 MSA, 47 PD, 7 LBD, 17 AD, 8 PSP, 5 CBD, 43 HCs (autopsy)

RT-QuIC, PMCA

66.7% (2/3) of MSA patients showed positive seeding activity

Donadio et al. [140]

8 MSA, 17 PD, 5 DLB, 3 PAF

RT-QuIC

Seeding activity from patients with synucleinopathies was higher than that of non-synucleinopathies

Olfactory mucosa

De Luca et al. [146]

11 MSA, 18 PD, 6 CBD, 12 PSP

RT-QuIC

81.8% (9/11) of MSA patients showed positive seeding activity

The biochemical and morphological features of α-syn aggregates were different between MSA and PD

Bargar et al. [147]

30 MSA, 13 PD, 11 HC

RT-QuIC

90% (18/20) of MSA-P and only 10% (1/10) of MSA-C patients showed positive seeding activity

Seeding activity positively correlated with rigidity and postural instability

De Luca et al. [148]

2 MSA, 2 PD, 1 HC

RT-QuIC

100% (2/2) of MSA patients showed positive seeding activity

The biochemical and morphological features of α-syn aggregates were different between MSA and PD

  1. AD Alzheimer disease, CBD corticobasal degeneration, CBS corticobasal syndrome, DLB dementia with Lewy bodies, HC healthy control, iRBD Idiopathic REM sleep behaviour disorder, MSA multiple system atrophy, PAF pure autonomic failure, PD Parkinson’s disease, PMCA protein misfolding cyclic amplification, PSP progressive supranuclear palsy, RT-QuIC real-time quaking-induced conversion