Holm Nielsen Signe, Møller Hausgaard Cecilie, Benmarce Meryem, Karsdal Morten, Henriksen Kim
Nordic Bioscience, Herlev, Denmark.
Technical University of Denmark, Lyngby, Denmark.
Sci Rep. 2025 Apr 9;15(1):12081. doi: 10.1038/s41598-025-92726-x.
Parkinson's disease (PD) is a progressive neurodegenerative condition. One of the unmet medical needs in PD, are tools for better diagnosis, prognosis, and efficacy of treatment, which reflects the disease course of the individual patient. Alpha-Synuclein (α-Synuclein) is a hallmark of synucleinopathies such as PD, where α-Synuclein aggregates are deposited. Calpain-1 is an enzyme, located in the presynaptic terminal, and shown to be active as an early event related to aggregation of α-Synuclein. The aim of this study was to develop and evaluate a competitive ELISA, targeting a Calpain-1 specific cleavage site of α-Synuclein, named α-Syn-C, and evaluate it in serum from patients diagnosed with PD and comparing to healthy matched donors. A monoclonal antibody was raised against the α-Synuclein fragment generated by cleavage of Calpain-1 and employed in an ELISA assay. The assay was developed, technically evaluated, and quantified in two independent cohorts of patients diagnosed with PD and compared to the healthy donors. The discovery cohort showed α-Syn-C was significantly upregulated in patients with PD compared to healthy donors (p =0.0007), with a diagnostic value of AUC = 0.83. The evaluation cohort showed similar results with an ability to differentiate PD patients from healthy donors (p < 0.0001) with an AUC = 0.85. These findings are exploratory and hypothesis generating, indicating the α-Syn-C biomarker may be useful in managing PD patients, and needs to be validated in larger cohorts and longitudinal studies.
帕金森病（PD）是一种进行性神经退行性疾病。PD尚未满足的医疗需求之一是用于更好地诊断、预后评估和治疗效果评估的工具，这些工具能够反映个体患者的疾病进程。α-突触核蛋白（α-Synuclein）是帕金森病等突触核蛋白病的一个标志，其中α-突触核蛋白聚集体会沉积。钙蛋白酶-1是一种位于突触前末端的酶，已被证明作为与α-突触核蛋白聚集相关的早期事件具有活性。本研究的目的是开发并评估一种竞争性酶联免疫吸附测定（ELISA），该测定针对α-突触核蛋白的钙蛋白酶-1特异性切割位点，命名为α-Syn-C，并在被诊断为帕金森病的患者血清中进行评估，同时与健康匹配的供体进行比较。针对钙蛋白酶-1切割产生的α-突触核蛋白片段制备了单克隆抗体，并用于ELISA检测。该检测方法在两个独立的被诊断为帕金森病的患者队列中进行了开发、技术评估和定量分析，并与健康供体进行了比较。发现队列显示，与健康供体相比，帕金森病患者的α-Syn-C显著上调（p = 0.0007），诊断价值的曲线下面积（AUC）= 0.83。评估队列显示了相似的结果，能够区分帕金森病患者和健康供体（p < 0.0001），AUC = 0.85。这些发现具有探索性且能产生假设，表明α-Syn-C生物标志物可能有助于管理帕金森病患者，并且需要在更大的队列和纵向研究中进行验证。
