Carrazana Elizabeth, Montalbán-Gutiérrez Leonardo, Chana-Cuevas Pedro, Salvadores Natalia
Neurodegenerative Diseases Laboratory, Center for Biomedicine, Universidad Mayor, Avenida Alemania 0281, 4780000, Temuco, La Araucanía, Chile.
Escuela de Medicina, Facultad de Medicina y Ciencias de La Salud, Universidad Mayor, Temuco, Chile.
Mol Cell Biochem. 2025 Jun;480(6):3297-3314. doi: 10.1007/s11010-024-05190-y. Epub 2025 Jan 6.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by tremor, rigidity, and bradykinesia, beginning with early loss of dopaminergic neurons in the ventrolateral substantia nigra and advancing to broader neurodegeneration in the midbrain. The clinical heterogeneity of PD and the lack of specific diagnostic tests present significant challenges, highlighting the need for reliable biomarkers for early diagnosis. Alpha-synuclein (α-Syn), a protein aggregating into Lewy bodies and neurites in PD patients, has emerged as a key biomarker due to its central role in PD pathophysiology and potential to reflect pathological processes. Additionally, α-Syn allows earlier differentiation between PD and other neurodegenerative disorders with similar symptoms. Currently, detection of α-Syn pathology in post-mortem brain tissue remains the primary means of achieving a conclusive diagnosis, often revealing significant misdiagnoses. Seed amplification assay (SAA), initially developed for prion diseases, has been adapted to detect α-Syn aggregates in cerebrospinal fluid, showing promise for early diagnosis. Recent studies have demonstrated that SAA can also detect α-Syn aggregates in peripheral samples collected via minimally invasive procedures, such as skin, olfactory mucosa, saliva, and blood. However, the lack of standardized protocols limits clinical application. Standardizing protocols is essential to improve assay reliability and enable accurate patient identification for emerging therapies. This review examines studies on SAA for detecting α-Syn aggregates in minimally invasive samples, focusing on sample collection, processing, and reaction conditions.
帕金森病（PD）是一种进行性神经退行性疾病，其特征为震颤、僵硬和运动迟缓，始于腹外侧黑质多巴胺能神经元的早期丧失，并发展为中脑更广泛的神经退行性变。PD的临床异质性以及缺乏特异性诊断测试带来了重大挑战，凸显了对早期诊断可靠生物标志物的需求。α-突触核蛋白（α-Syn）是一种在PD患者中聚集成路易小体和神经突的蛋白质，由于其在PD病理生理学中的核心作用以及反映病理过程的潜力，已成为一种关键生物标志物。此外，α-Syn有助于更早地区分PD与其他具有相似症状的神经退行性疾病。目前，在死后脑组织中检测α-Syn病理仍然是实现确定性诊断的主要手段，但常常会出现重大误诊。种子扩增分析（SAA）最初是为朊病毒疾病开发的，现已被用于检测脑脊液中的α-Syn聚集体，显示出早期诊断的前景。最近的研究表明，SAA还可以检测通过微创程序收集的外周样本中的α-Syn聚集体，如皮肤、嗅黏膜、唾液和血液。然而，缺乏标准化方案限制了其临床应用。标准化方案对于提高检测可靠性和为新兴疗法准确识别患者至关重要。本综述考察了关于SAA检测微创样本中α-Syn聚集体的研究，重点关注样本采集、处理和反应条件。
