Discrimination of MSA-P and MSA-C by RT-QuIC analysis of olfactory mucosa: the first assessment of assay reproducibility between two specialized laboratories.
Alpha-synuclein
Biomarkers
Misfolding
Olfactory mucosa
Real-Time Quaking-Induced Conversion
Journal
Molecular neurodegeneration
ISSN: 1750-1326
Titre abrégé: Mol Neurodegener
Pays: England
ID NLM: 101266600
Informations de publication
Date de publication:
11 12 2021
11 12 2021
Historique:
received:
03
05
2021
accepted:
13
09
2021
entrez:
13
12
2021
pubmed:
14
12
2021
medline:
5
4
2022
Statut:
epublish
Résumé
Detection of the pathological and disease-associated alpha-synuclein (αSyn OM samples were prospectively collected from patients with a probable diagnosis of MSA-P (n = 20, mean disease duration 4.4 years), MSA-C (n = 10, mean disease duration 4 years), PD (n = 13, mean disease duration 8 years), and healthy control subjects (HS) (n = 11). Each sample was analyzed by αSyn_RT-QuIC in two independent specialized laboratories, one located in Italy (ITA-lab) and one located in the USA (USA-lab). Both laboratories have developed and used harmonized αSyn_RT-QuIC analytical procedures. Results were correlated with demographic and clinical data. The αSyn_RT-QuIC analysis reached a 96% interrater agreement of results (IAR) between laboratories (Kappa = 0.93, 95% CI 0.83-1.00). In particular, αSyn_RT-QuIC seeding activity was found in the OM of 9/13 patients with PD (sensitivity 69%, IAR 100%) and 18/20 patients with MSA-P (sensitivity 90%, IAR 100%). Interestingly, samples collected from patients with MSA-C did not induce αSyn_RT-QuIC seeding activity, except for one subject in USA-lab. Therefore, we found that MSA-P and MSA-C induced opposite effects. Regardless of disease diagnosis, the αSyn_RT-QuIC seeding activity correlated with some clinical parameters, including the rigidity and postural instability. Our study provides evidence that OM-αSyn
Sections du résumé
BACKGROUND
Detection of the pathological and disease-associated alpha-synuclein (αSyn
METHODS
OM samples were prospectively collected from patients with a probable diagnosis of MSA-P (n = 20, mean disease duration 4.4 years), MSA-C (n = 10, mean disease duration 4 years), PD (n = 13, mean disease duration 8 years), and healthy control subjects (HS) (n = 11). Each sample was analyzed by αSyn_RT-QuIC in two independent specialized laboratories, one located in Italy (ITA-lab) and one located in the USA (USA-lab). Both laboratories have developed and used harmonized αSyn_RT-QuIC analytical procedures. Results were correlated with demographic and clinical data.
RESULTS
The αSyn_RT-QuIC analysis reached a 96% interrater agreement of results (IAR) between laboratories (Kappa = 0.93, 95% CI 0.83-1.00). In particular, αSyn_RT-QuIC seeding activity was found in the OM of 9/13 patients with PD (sensitivity 69%, IAR 100%) and 18/20 patients with MSA-P (sensitivity 90%, IAR 100%). Interestingly, samples collected from patients with MSA-C did not induce αSyn_RT-QuIC seeding activity, except for one subject in USA-lab. Therefore, we found that MSA-P and MSA-C induced opposite effects. Regardless of disease diagnosis, the αSyn_RT-QuIC seeding activity correlated with some clinical parameters, including the rigidity and postural instability.
CONCLUSIONS
Our study provides evidence that OM-αSyn
Identifiants
pubmed: 34895275
doi: 10.1186/s13024-021-00491-y
pii: 10.1186/s13024-021-00491-y
pmc: PMC8665327
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
82Subventions
Organisme : NIA NIH HHS
ID : R01 AG057557
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS112010
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG062272
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061388
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS118760
Pays : United States
Organisme : US National Institutes of Health (NIH)/National Institute on Aging
ID : R01AG061388
Informations de copyright
© 2021. The Author(s).
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