Baseline concentration of misfolded α-synuclein aggregates in cerebrospinal fluid predicts risk of cognitive decline in Parkinson's disease.
Parkinson disease
alpha-synuclein
cognitive decline
dementia
protein misfolding cyclic amplification
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
25
06
2018
accepted:
15
10
2018
pubmed:
23
10
2018
medline:
22
8
2020
entrez:
23
10
2018
Statut:
ppublish
Résumé
The prognostic significance of misfolded α-synuclein (α-Syn) aggregates in Parkinson's disease (PD) has not been well investigated. The aim of this study was to reveal the relationship between misfolded α-Syn aggregate concentration in cerebrospinal fluid (CSF) and cognitive decline risk in PD. A total of 278 patients with PD were retrospectively included. They were diagnosed between 2011 and 2013. The end-point was 2016, and the follow-up period was 54.3 ± 10.0 months. Cognitive decline was defined as a 4-point decrease in the Mini-Mental State Examination score during follow-up. Misfolded α-Syn aggregate concentration in baseline CSF was measured using the protein misfolding cyclic amplification (PMCA) technique. Time to reach 50% of the maximum fluorescence value was recorded. The PMCA technique successfully detected the level of misfolded α-Syn aggregates in CSF with a sensitivity of 85.3% and a specificity of 91.4%. The time to reach 50% of the maximum fluorescence value was shorter in the patients with cognitive decline than in the patients without cognitive decline (190.7 ± 40.1 h vs. 240.8 ± 45.6 h, P < 0.001). Multifactorial Cox regression analysis revealed that reaching 50% of the maximum fluorescence value in ≤219 h at baseline was associated with increased risk of cognitive decline during the follow-up (HR: 4.90, 95% CI: 2.75-8.74, P < 0.001). Baseline concentration of misfolded α-Syn aggregates in CSF measured by the PMCA technique predicts risk of cognitive decline in PD.
Sections du résumé
BACKGROUND
The prognostic significance of misfolded α-synuclein (α-Syn) aggregates in Parkinson's disease (PD) has not been well investigated. The aim of this study was to reveal the relationship between misfolded α-Syn aggregate concentration in cerebrospinal fluid (CSF) and cognitive decline risk in PD.
METHODS
A total of 278 patients with PD were retrospectively included. They were diagnosed between 2011 and 2013. The end-point was 2016, and the follow-up period was 54.3 ± 10.0 months. Cognitive decline was defined as a 4-point decrease in the Mini-Mental State Examination score during follow-up. Misfolded α-Syn aggregate concentration in baseline CSF was measured using the protein misfolding cyclic amplification (PMCA) technique. Time to reach 50% of the maximum fluorescence value was recorded.
RESULTS
The PMCA technique successfully detected the level of misfolded α-Syn aggregates in CSF with a sensitivity of 85.3% and a specificity of 91.4%. The time to reach 50% of the maximum fluorescence value was shorter in the patients with cognitive decline than in the patients without cognitive decline (190.7 ± 40.1 h vs. 240.8 ± 45.6 h, P < 0.001). Multifactorial Cox regression analysis revealed that reaching 50% of the maximum fluorescence value in ≤219 h at baseline was associated with increased risk of cognitive decline during the follow-up (HR: 4.90, 95% CI: 2.75-8.74, P < 0.001).
CONCLUSION
Baseline concentration of misfolded α-Syn aggregates in CSF measured by the PMCA technique predicts risk of cognitive decline in PD.
Identifiants
pubmed: 30346044
doi: 10.1111/nan.12524
pmc: PMC7380054
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
alpha-Synuclein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
398-409Informations de copyright
© 2018 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
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