Cargando…

A Panel of Plasma Biomarkers for Differential Diagnosis of Parkinsonian Syndromes

OBJECTIVE: The aim of our study is to explore the most reliable panel of plasma biomarkers for differential diagnosis of parkinsonian syndromes (PDSs). We selected five kinds of neurodegenerative proteins in plasma: neurofilament light chain (NfL), α-synuclein (α-syn), total tau, β-amyloid 42 (Aβ42)...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Qi, Li, Zhen, Han, Xiaoxuan, Shen, Xiao, Wang, Fei, Bai, Lipeng, Li, Zhuo, Zhang, Rui, Wang, Yanlin, Zhu, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891509/
https://www.ncbi.nlm.nih.gov/pubmed/35250451
http://dx.doi.org/10.3389/fnins.2022.805953
_version_ 1784661898878255104
author Li, Qi
Li, Zhen
Han, Xiaoxuan
Shen, Xiao
Wang, Fei
Bai, Lipeng
Li, Zhuo
Zhang, Rui
Wang, Yanlin
Zhu, Xiaodong
author_facet Li, Qi
Li, Zhen
Han, Xiaoxuan
Shen, Xiao
Wang, Fei
Bai, Lipeng
Li, Zhuo
Zhang, Rui
Wang, Yanlin
Zhu, Xiaodong
author_sort Li, Qi
collection PubMed
description OBJECTIVE: The aim of our study is to explore the most reliable panel of plasma biomarkers for differential diagnosis of parkinsonian syndromes (PDSs). We selected five kinds of neurodegenerative proteins in plasma: neurofilament light chain (NfL), α-synuclein (α-syn), total tau, β-amyloid 42 (Aβ42) and β-amyloid 40 (Aβ40), and investigated the diagnostic value of these biomarkers. METHODS: A total of 99 plasma samples from patients with Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy, and age-matched healthy controls (HCs) were enrolled in our study. Plasma NfL, α-syn, total tau, Aβ42, and Aβ40 levels were quantified by ultrasensitive single molecule array immunoassay. We used logistic regression analyses to examine diagnostic accuracy of these plasma biomarkers. Disease severity was assessed by the modified Hoehn and Yahr staging scale, Unified Parkinson’s Disease Rating Scale part III (UPDRS III), and the Mini-Mental State Examination (MMSE), and subsequently, correlation analysis was performed. RESULTS: A combination of α-syn, Aβ42, Aβ40, Aβ42/40, and NfL could achieve a best diagnostic value in differentiating PDSs from HC and PD from HC, with an AUC of 0.983 and 0.977, respectively. By adding NfL to measurements of α-syn or Aβ42 or Aβ40 or Aβ42/40, the best discriminating panel was formed in differentiating atypical parkinsonian disorder (APD) and HC, and the discriminatory potential could reach a sensitivity of 100% and specificity of 100% (AUC = 1.000). For further distinguishing PD from APD, we found a combination of NfL, Aβ42, and total tau was the most reliable panel with equally high diagnostic accuracy. With respect to differentiating the subtypes of APD from one another, our results revealed that measurement of NfL, total tau, Aβ42, Aβ40, and Aβ42/40 was the best discriminating panel. Correlation analysis suggests that plasma Aβ42 levels were positively correlated to UPDRS part III scores in MSA. In terms of cognitive function, there was a relationship between plasma Aβ42/40 level and MMSE scores in patients with APD. CONCLUSION: In our study, various combinations of plasma biomarkers have great potentialities in identifying PDSs, with important clinical utility in improving diagnostic accuracy. Plasma NfL may have added value to a blood-based biomarker panel for differentiating PDSs.
format Online
Article
Text
id pubmed-8891509
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-88915092022-03-04 A Panel of Plasma Biomarkers for Differential Diagnosis of Parkinsonian Syndromes Li, Qi Li, Zhen Han, Xiaoxuan Shen, Xiao Wang, Fei Bai, Lipeng Li, Zhuo Zhang, Rui Wang, Yanlin Zhu, Xiaodong Front Neurosci Neuroscience OBJECTIVE: The aim of our study is to explore the most reliable panel of plasma biomarkers for differential diagnosis of parkinsonian syndromes (PDSs). We selected five kinds of neurodegenerative proteins in plasma: neurofilament light chain (NfL), α-synuclein (α-syn), total tau, β-amyloid 42 (Aβ42) and β-amyloid 40 (Aβ40), and investigated the diagnostic value of these biomarkers. METHODS: A total of 99 plasma samples from patients with Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy, and age-matched healthy controls (HCs) were enrolled in our study. Plasma NfL, α-syn, total tau, Aβ42, and Aβ40 levels were quantified by ultrasensitive single molecule array immunoassay. We used logistic regression analyses to examine diagnostic accuracy of these plasma biomarkers. Disease severity was assessed by the modified Hoehn and Yahr staging scale, Unified Parkinson’s Disease Rating Scale part III (UPDRS III), and the Mini-Mental State Examination (MMSE), and subsequently, correlation analysis was performed. RESULTS: A combination of α-syn, Aβ42, Aβ40, Aβ42/40, and NfL could achieve a best diagnostic value in differentiating PDSs from HC and PD from HC, with an AUC of 0.983 and 0.977, respectively. By adding NfL to measurements of α-syn or Aβ42 or Aβ40 or Aβ42/40, the best discriminating panel was formed in differentiating atypical parkinsonian disorder (APD) and HC, and the discriminatory potential could reach a sensitivity of 100% and specificity of 100% (AUC = 1.000). For further distinguishing PD from APD, we found a combination of NfL, Aβ42, and total tau was the most reliable panel with equally high diagnostic accuracy. With respect to differentiating the subtypes of APD from one another, our results revealed that measurement of NfL, total tau, Aβ42, Aβ40, and Aβ42/40 was the best discriminating panel. Correlation analysis suggests that plasma Aβ42 levels were positively correlated to UPDRS part III scores in MSA. In terms of cognitive function, there was a relationship between plasma Aβ42/40 level and MMSE scores in patients with APD. CONCLUSION: In our study, various combinations of plasma biomarkers have great potentialities in identifying PDSs, with important clinical utility in improving diagnostic accuracy. Plasma NfL may have added value to a blood-based biomarker panel for differentiating PDSs. Frontiers Media S.A. 2022-02-17 /pmc/articles/PMC8891509/ /pubmed/35250451 http://dx.doi.org/10.3389/fnins.2022.805953 Text en Copyright © 2022 Li, Li, Han, Shen, Wang, Bai, Li, Zhang, Wang and Zhu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Li, Qi
Li, Zhen
Han, Xiaoxuan
Shen, Xiao
Wang, Fei
Bai, Lipeng
Li, Zhuo
Zhang, Rui
Wang, Yanlin
Zhu, Xiaodong
A Panel of Plasma Biomarkers for Differential Diagnosis of Parkinsonian Syndromes
title A Panel of Plasma Biomarkers for Differential Diagnosis of Parkinsonian Syndromes
title_full A Panel of Plasma Biomarkers for Differential Diagnosis of Parkinsonian Syndromes
title_fullStr A Panel of Plasma Biomarkers for Differential Diagnosis of Parkinsonian Syndromes
title_full_unstemmed A Panel of Plasma Biomarkers for Differential Diagnosis of Parkinsonian Syndromes
title_short A Panel of Plasma Biomarkers for Differential Diagnosis of Parkinsonian Syndromes
title_sort panel of plasma biomarkers for differential diagnosis of parkinsonian syndromes
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891509/
https://www.ncbi.nlm.nih.gov/pubmed/35250451
http://dx.doi.org/10.3389/fnins.2022.805953
work_keys_str_mv AT liqi apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT lizhen apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT hanxiaoxuan apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT shenxiao apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT wangfei apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT bailipeng apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT lizhuo apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT zhangrui apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT wangyanlin apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT zhuxiaodong apanelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT liqi panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT lizhen panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT hanxiaoxuan panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT shenxiao panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT wangfei panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT bailipeng panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT lizhuo panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT zhangrui panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT wangyanlin panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes
AT zhuxiaodong panelofplasmabiomarkersfordifferentialdiagnosisofparkinsoniansyndromes