Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Department of Radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Eur J Neurol. 2022 Dec;29(12):3590-3599. doi: 10.1111/ene.15537. Epub 2022 Sep 15.
The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD.
In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system.
It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p < 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p < 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes.
Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.
帕金森病（PD）的隐匿发病使其早期诊断变得困难。值得注意的是，特发性快速眼动睡眠行为障碍（iRBD）被报道为 PD 的前驱期，这可能代表了 PD 早期诊断的一个突破。然而，目前尚无可靠的 PD 诊断生物标志物。鉴于α-突触核蛋白（α-Syn）和神经炎症在 PD 临床症状出现之前就已经发展，因此假设血浆总外泌体α-Syn（t-exo α-Syn）、神经源性外泌体α-Syn（n-exo α-Syn）和外泌体凋亡相关斑点样蛋白含有半胱氨酸天冬氨酸蛋白酶激活和募集结构域（ASC）可能是 PD 的潜在生物标志物。
本研究纳入了 78 例 PD 患者、153 例可能的 iRBD 患者（pRBD）和 63 名健康对照者（HCs）。采用一步法基于顺磁微粒的化学发光免疫分析法测定 α-Syn 浓度，采用 Ella 系统测定 ASC 水平。
与 pRBD 和 HCs 组相比，PD 组的 t-exo α-Syn 显著升高（p<0.0001），而 PD 和 pRBD 组的 n-exo α-Syn 水平均显著高于 HCs 组（p<0.0001）。此外，虽然 PD 和 pRBD 组之间 ASC 水平无差异，但外泌体中 ASC 与 α-Syn 呈正相关。
本研究结果提示，PD 组的 t-exo α-Syn 和 n-exo α-Syn 均升高，而 pRBD 组仅 n-exo α-Syn 升高。此外，炎症小体衔接蛋白 ASC 与 α-Syn 相关，可能促进突触核蛋白病的发生。
