α‐Synuclein species in plasma neuron‐derived extracellular vesicles as biomarkers for iRBD

Abstract Objective Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α‐Synuclein...

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Main Authors: Xuemei Wang, Yuanchu Zheng, Huihui Cai, Wenyi Kou, Chen Yang, Siming Li, Bingxu Zhu, Jiayi Wu, Ning Zhang, Tao Feng, Xiaohong Li, Fulong Xiao, Zhenwei Yu
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Annals of Clinical and Translational Neurology
Online Access:https://doi.org/10.1002/acn3.52200
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author Xuemei Wang
Yuanchu Zheng
Huihui Cai
Wenyi Kou
Chen Yang
Siming Li
Bingxu Zhu
Jiayi Wu
Ning Zhang
Tao Feng
Xiaohong Li
Fulong Xiao
Zhenwei Yu
author_facet Xuemei Wang
Yuanchu Zheng
Huihui Cai
Wenyi Kou
Chen Yang
Siming Li
Bingxu Zhu
Jiayi Wu
Ning Zhang
Tao Feng
Xiaohong Li
Fulong Xiao
Zhenwei Yu
author_sort Xuemei Wang
collection DOAJ
description Abstract Objective Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α‐Synuclein (α‐Syn) species in plasma neuron‐derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs). Methods Nanoscale flow cytometry was used to detect α‐Syn‐containing NDEVs in plasma. Results A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α‐Syn, α‐Syn aggregates, and phosphorylated α‐Syn at Ser129 (pS129)‐containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (p < 0.0001 for all). In distinguishing between iRBD and HCs, the area under the receiver operating characteristic (ROC) curve (AUC) for an integrative model incorporating the levels of α‐Syn, pS129, and α‐Syn aggregate‐containing NDEVs in plasma was 0.965. This model achieved a sensitivity of 94.3% and a specificity of 88.9%. In iRBD group, the concentrations of α‐Syn aggregate‐containing NDEVs exhibited a negative correlation with Sniffin’ Sticks olfactory scores (r = −0.351, p = 0.039). Smokers with iRBD exhibited lower levels of α‐Syn aggregates and pS129‐containing NDEVs in plasma compared to nonsmokers (pα‐Syn aggregates = 0.014; ppS129 = 0.003). Interpretation The current study demonstrated that the levels of total α‐Syn, α‐Syn aggregates, and pS129‐containing NDEVs in the plasma of individuals with iRBD were significantly higher compared to HCs. The levels of α‐Syn species‐containing NDEVs in plasma may serve as biomarkers for iRBD.
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spelling doaj-art-9a3681aa12b44698a6377536c3bc80db2024-11-18T17:52:33ZengWileyAnnals of Clinical and Translational Neurology2328-95032024-11-0111112891290310.1002/acn3.52200α‐Synuclein species in plasma neuron‐derived extracellular vesicles as biomarkers for iRBDXuemei Wang0Yuanchu Zheng1Huihui Cai2Wenyi Kou3Chen Yang4Siming Li5Bingxu Zhu6Jiayi Wu7Ning Zhang8Tao Feng9Xiaohong Li10Fulong Xiao11Zhenwei Yu12Center for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaCenter for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaCenter for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaCenter for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaCenter for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaCenter for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaCenter for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaCenter for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neuropsychiatry and Behavioral Neurology and Clinical Psychology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaCenter for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Affiliated Dalian Municipal Friendship Hospital of Dalian Medical University Dalian ChinaDivision of Sleep Medicine Peking University People's Hospital Beijing ChinaDepartment of Pathophysiology Beijing Neurosurgical Institute, Capital Medical University Beijing ChinaAbstract Objective Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α‐Synuclein (α‐Syn) species in plasma neuron‐derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs). Methods Nanoscale flow cytometry was used to detect α‐Syn‐containing NDEVs in plasma. Results A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α‐Syn, α‐Syn aggregates, and phosphorylated α‐Syn at Ser129 (pS129)‐containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (p < 0.0001 for all). In distinguishing between iRBD and HCs, the area under the receiver operating characteristic (ROC) curve (AUC) for an integrative model incorporating the levels of α‐Syn, pS129, and α‐Syn aggregate‐containing NDEVs in plasma was 0.965. This model achieved a sensitivity of 94.3% and a specificity of 88.9%. In iRBD group, the concentrations of α‐Syn aggregate‐containing NDEVs exhibited a negative correlation with Sniffin’ Sticks olfactory scores (r = −0.351, p = 0.039). Smokers with iRBD exhibited lower levels of α‐Syn aggregates and pS129‐containing NDEVs in plasma compared to nonsmokers (pα‐Syn aggregates = 0.014; ppS129 = 0.003). Interpretation The current study demonstrated that the levels of total α‐Syn, α‐Syn aggregates, and pS129‐containing NDEVs in the plasma of individuals with iRBD were significantly higher compared to HCs. The levels of α‐Syn species‐containing NDEVs in plasma may serve as biomarkers for iRBD.https://doi.org/10.1002/acn3.52200
spellingShingle Xuemei Wang
Yuanchu Zheng
Huihui Cai
Wenyi Kou
Chen Yang
Siming Li
Bingxu Zhu
Jiayi Wu
Ning Zhang
Tao Feng
Xiaohong Li
Fulong Xiao
Zhenwei Yu
α‐Synuclein species in plasma neuron‐derived extracellular vesicles as biomarkers for iRBD
Annals of Clinical and Translational Neurology
title α‐Synuclein species in plasma neuron‐derived extracellular vesicles as biomarkers for iRBD
title_full α‐Synuclein species in plasma neuron‐derived extracellular vesicles as biomarkers for iRBD
title_fullStr α‐Synuclein species in plasma neuron‐derived extracellular vesicles as biomarkers for iRBD
title_full_unstemmed α‐Synuclein species in plasma neuron‐derived extracellular vesicles as biomarkers for iRBD
title_short α‐Synuclein species in plasma neuron‐derived extracellular vesicles as biomarkers for iRBD
title_sort α synuclein species in plasma neuron derived extracellular vesicles as biomarkers for irbd
url https://doi.org/10.1002/acn3.52200
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