Propagative α-synuclein seeds as serum biomarkers for synucleinopathies.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
01
07
2022
accepted:
21
04
2023
medline:
26
6
2023
pubmed:
30
5
2023
entrez:
29
5
2023
Statut:
ppublish
Résumé
Abnormal α-synuclein aggregation is a key pathological feature of a group of neurodegenerative diseases known as synucleinopathies, which include Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA). The pathogenic β-sheet seed conformation of α-synuclein is found in various tissues, suggesting potential as a biomarker, but few studies have been able to reliably detect these seeds in serum samples. In this study, we developed a modified assay system, called immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), which enables the detection of pathogenic α-synuclein seeds in the serum of individuals with synucleinopathies. In our internal first and second cohorts, IP/RT-QuIC showed high diagnostic performance for differentiating PD versus controls (area under the curve (AUC): 0.96 (95% confidence interval (CI) 0.95-0.99)/AUC: 0.93 (95% CI 0.84-1.00)) and MSA versus controls (AUC: 0.64 (95% CI 0.49-0.79)/AUC: 0.73 (95% CI 0.49-0.98)). IP/RT-QuIC also showed high diagnostic performance in differentiating individuals with PD (AUC: 0.86 (95% CI 0.74-0.99)) and MSA (AUC: 0.80 (95% CI 0.65-0.97)) from controls in a blinded external cohort. Notably, amplified seeds maintained disease-specific properties, allowing the differentiation of samples from individuals with PD versus MSA. In summary, here we present a novel platform that may allow the detection of individuals with synucleinopathies using serum samples.
Identifiants
pubmed: 37248302
doi: 10.1038/s41591-023-02358-9
pii: 10.1038/s41591-023-02358-9
pmc: PMC10287557
doi:
Substances chimiques
alpha-Synuclein
0
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1448-1455Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : 21dm0207070
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : 21wm0425015
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 21H04820
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 19K16928
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 21K07424
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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