Parkinson's disease (PD), being the second largest neurodegenerative disease, poses challenges in early detection, resulting in a lack of timely treatment options to effectively manage the disease. By the time clinical diagnosis becomes possible, more than 60% of dopamine neurons in the substantia nigra (SN) of patients have already degenerated. Therefore, early diagnosis or identification of warning signs is crucial for the prompt and timely beginning of the treatment. However, conducting invasive or complex diagnostic procedures on asymptomatic patients can be challenging, making routine blood tests a more feasible approach in such cases. Numerous studies have been conducted over an extended period to search for effective diagnostic biomarkers in blood samples. However, thus far, no highly effective biomarkers have been confirmed. Besides classical proteins like α‐synuclein (α‐syn), phosphorylated α‐syn and oligomeric α‐syn, other molecules involved in disease progression should also be given equal attention. In this review, we will not only discuss proposed biomarkers that are currently under investigation but also delve into the mechanisms underlying the disease, focusing on processes such as α‐syn misfolding, intercellular transmission and the crossing of the blood–brain barrier (BBB). Our aim is to provide an updated overview of molecules based on these processes that may potentially serve as blood biomarkers.

中文翻译：

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我们距离突破还有多远？寻找帕金森病诊断中的血液生物标志物

帕金森病（PD）是第二大神经退行性疾病，对早期发现提出了挑战，导致缺乏及时的治疗方案来有效控制该疾病。当临床诊断成为可能时，患者黑质（SN）中超过60%的多巴胺神经元已经退化。因此，早期诊断或识别预警信号对于及时、及时开始治疗至关重要。然而，对无症状患者进行侵入性或复杂的诊断程序可能具有挑战性，这使得常规血液检测在这种情况下成为更可行的方法。为了在血液样本中寻找有效的诊断生物标志物，已经进行了很长一段时间的大量研究。然而，迄今为止，尚未证实高效的生物标志物。除了α-突触核蛋白（α-syn）、磷酸化α-syn和寡聚α-syn等经典蛋白质外，其他参与疾病进展的分子也应受到同等关注。在这篇综述中，我们不仅将讨论目前正在研究的拟议生物标志物，还将深入研究疾病背后的机制，重点关注α-syn错误折叠、细胞间传播和穿越血脑屏障（BBB）等过程。我们的目标是根据这些可能作为血液生物标志物的过程提供分子的最新概述。