α-突触核蛋白检测在帕金森病诊断中的应用

Application of α-Synuclein Detection in the Diagnosis of Parkinson’s Disease

摘要: 帕金森病(Parkinson’s disease, PD)是全球第二大神经退行性疾病，传统诊断主要依赖临床症状学评估，存在误诊、漏诊和早期诊断困难等问题。病理性α-突触核蛋白(α-synuclein, α-syn)的聚集是PD的核心病理特征，在脑脊液、皮肤、血液等多种生物样本中均可检出，为开发分子诊断标志物奠定了基础。α-syn检测技术经历了从总量测定到构象特异性识别的演进，其中，脑脊液种子扩增检测(seed amplification assay, SAA)在临床研究中表现出优异的诊断效能，但腰椎穿刺的侵入性限制其临床推广；皮肤活检虽提供了神经病理的外周窗口，但处理流程复杂、操作依赖性强；血液检测最具临床推广潜力，新兴的单分子成像技术通过直接观察病理聚集体、构象特异性识别等优势，有望突破红细胞干扰和低浓度检测等瓶颈。本文围绕α-syn检测技术在PD诊断中的应用现状与进展进行综述，系统梳理各技术的原理、在不同样本中的诊断效能及临床转化前景，为推动PD诊断从症状学评估向无创、精准的分子诊断转变提供参考。

Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, with traditional diagnosis relying on clinical symptomatology, which suffers from difficulty in early detection and high rates of misdiagnosis. Pathological α-synuclein (α-syn) aggregation is the hallmark neuropathology of PD and can be detected in multiple biological specimens including cerebrospinal fluid (CSF), skin, and blood, providing a molecular basis for biomarker development. Detection methodologies for α-syn have evolved from quantification of total α-syn to conformation-specific recognition. Among these, CSF seed amplification assay (SAA) demonstrates excellent diagnostic accuracy in clinical research but is limited by the invasiveness of lumbar puncture. Skin biopsy offers a peripheral neuropathological window, yet the processing procedures are complex and operator-dependent. Blood-based detection shows the greatest clinical potential. Emerging single-molecule imaging techniques show promise for overcoming red blood cell interference and low-concentration detection challenges through direct visualization of pathological aggregates and conformation-specific recognition. This review comprehensively summarizes the current status and advances of α-syn detection techniques in PD diagnosis. We elucidate the principles of various methods, their diagnostic performance in different samples, and prospects for clinical translation, providing insights to advance PD diagnostics from symptom-based assessment toward non-invasive, precision molecular diagnosis.