Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson’s disease (PD) pathology. β-Glucocerebrosidase (GCase) has also been reported to be correlated with α-synuclein (α-syn) proteostasis. However, lncRNAs and α-syn in neural-derived L1CAM exosomes and GCase activity in the plasma of PD patients have not been studied. This study used an ultrasensitive methodology, fluorescence nanoparticle tracking analysis (NTA), to measure plasma L1CAM exosomes and Quanterix Simoa to measure α-syn concentrations in L1CAM exosomes. Eighty-five healthy controls and 93 PD patients were enrolled, and several scales were used to rate the severity of PD. Receiver operating characteristic (ROC) curves were applied to map the diagnostic accuracy of categorizing PD patients and healthy subjects. We found increased Linc-POU3F3 and α-syn concentrations in L1CAM exosomes and decreased GCase activity in PD patients compared with controls. The three biomarkers displayed obvious differences among PD patients based on gender, H-Y stage, and UPDRS-III distribution. Interestingly, Linc-POU3F3 was significantly positively correlated with α-syn in L1CAM exosomes and inversely correlated with GCase activity in PD patients. Significant correlations were observed among L1CAM exosomal Linc-POU3F3 levels, GCase activity, and PD severity, including motor/cognitive dysfunction. Additionally, the combination of Linc-POU3F3 and α-syn in L1CAM exosomes and GCase activity could discriminate PD patients from controls. These results suggest that L1CAM exosomal Linc-POU3F3, L1CAM exosomal α-syn, and GCase activity may shed light on the mechanism underlying the autophagic-lysosomal system in the pathogenesis of PD and could be used to assess the severity of PD.

长链非编码 RNA (lncRNA) 与自噬-溶酶体通路 (ALP) 相关，并且与帕金森病 (PD) 病理学密切相关。据报道，β-葡萄糖脑苷脂酶 (GCase) 也与 α-突触核蛋白 (α-syn) 蛋白稳态相关。然而，尚未研究神经来源的 L1CAM 外泌体中的 lncRNA 和 α-syn 以及 PD 患者血浆中的 GCase 活性。本研究使用超灵敏方法荧光纳米粒子追踪分析 (NTA) 来测量血浆 L1CAM 外泌体，并使用 Quanterix Simoa 测量 L1CAM 外泌体中的 α-syn 浓度。85 名健康对照者和 93 名 PD 患者入组，并使用多种量表对 PD 的严重程度进行评分。应用受试者工作特征 (ROC) 曲线来绘制对 PD 患者和健康受试者进行分类的诊断准确性。我们发现与对照组相比，PD 患者的 L1CAM 外泌体中 Linc-POU3F3 和 α-syn 浓度增加，GCase 活性降低。根据性别、HY分期和UPDRS-III分布，三种生物标志物在PD患者之间显示出明显差异。有趣的是，Linc-POU3F3 与 L1CAM 外泌体中的 α-syn 显着正相关，与 PD 患者的 GCase 活性呈负相关。在 L1CAM 外泌体 Linc-POU3F3 水平、GCase 活性和 PD 严重程度（包括运动/认知功能障碍）之间观察到显着相关性。此外，L1CAM 外泌体中的 Linc-POU3F3 和 α-syn 和 GCase 活性的组合可以将 PD 患者与对照组区分开来。这些结果表明 L1CAM 外泌体 Linc-POU3F3、L1CAM 外泌体 α-syn、