血浆神经元来源细胞外囊泡中的 α-突触核蛋白作为 iRBD 的生物标志物。

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

机构信息

Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Ann Clin Transl Neurol. 2024 Nov;11(11):2891-2903. doi: 10.1002/acn3.52200. Epub 2024 Sep 18.

DOI:10.1002/acn3.52200

PMID:39291779

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11572749/

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 (p = 0.014; p = 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.

摘要

目的

孤立性快速眼动睡眠行为障碍（iRBD）被认为是帕金森病（PD）最强的预测因子。目前急需可靠且准确的 iRBD 检测和表型转化预测生物标志物。本研究旨在探讨血浆神经元衍生细胞外囊泡（NDEVs）中α-突触核蛋白（α-Syn）的种类是否可以区分 iRBD 患者和健康对照（HCs）。

方法

使用纳米流式细胞术检测血浆中含α-Syn 的 NDEVs。

结果

共纳入 54 例 iRBD 患者和 53 例 HCs。iRBD 个体血浆中总α-Syn、α-Syn 聚集物和磷酸化α-Syn （Ser129）-含 NDEVs 的浓度明显高于 HCs（所有 p<0.0001）。在区分 iRBD 和 HCs 时，纳入α-Syn、pS129 和α-Syn 聚集物含 NDEVs 水平的综合模型的受试者工作特征（ROC）曲线下面积（AUC）为 0.965。该模型的灵敏度为 94.3%，特异性为 88.9%。在 iRBD 组中，α-Syn 聚集物含 NDEVs 的浓度与 Sniffin' Sticks 嗅觉评分呈负相关（r=-0.351，p=0.039）。与不吸烟者相比，iRBD 吸烟者的血浆中α-Syn 聚集物和 pS129 含 NDEVs 的水平较低（p=0.014；p=0.003）。