Kenzelmann Annalena, Boch Christina, Schmidt Ronny, Richter Mario, Schulz Michael
Quantitative, Translational and ADME Sciences, AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany.
Sciomics GmbH, Karl-Landsteiner Str. 6, 69151 Neckargemünd, Germany.
Biomedicines. 2024 Dec 9;12(12):2794. doi: 10.3390/biomedicines12122794.
BACKGROUND/OBJECTIVES: Neurodegenerative diseases are a major cause of morbidity and mortality worldwide, and their public health burden continues to increase. There is an urgent need to develop reliable and sensitive biomarkers to aid the timely diagnosis, disease progression monitoring, and therapeutic development for neurodegenerative disorders. Proteomic screening strategies, including antibody microarrays, are a powerful tool for biomarker discovery, but their findings should be confirmed using quantitative assays. The current study explored the feasibility of combining an exploratory proteomic strategy and confirmatory ligand-binding assays to screen for and validate biomarker candidates for neurodegenerative disorders.
It analyzed cerebrospinal fluid (CSF) and plasma samples from patients with Alzheimer's disease, Parkinson's disease, and multiple sclerosis and healthy controls using an exploratory antibody microarray and validatory ligand-binding assays.
The screening antibody microarray identified differentially expressed proteins between patients with neurodegenerative diseases and healthy controls, including cluster of differentiation 14 (CD14), osteopontin, and vascular endothelial growth factor 165b. Quantitative ligand-binding assays confirmed that CD14 levels were elevated in CSF of patients with Alzheimer's disease ( = 0.0177), whereas osteopontin levels were increased in CSF of patients with Parkinson's disease ( = 0.0346).
The current study demonstrated the potential utility of combining an exploratory proteomic approach and quantitative ligand-binding assays to identify biomarker candidates for neurodegenerative disorders. To further validate and expand these findings, large-scale analyses using well-characterized samples should be conducted.
背景/目的：神经退行性疾病是全球发病和死亡的主要原因，其公共卫生负担持续增加。迫切需要开发可靠且灵敏的生物标志物，以辅助神经退行性疾病的早期诊断、疾病进展监测及治疗开发。蛋白质组学筛选策略，包括抗体微阵列，是发现生物标志物的有力工具，但其结果应通过定量检测进行确认。本研究探讨了结合探索性蛋白质组学策略和确证性配体结合检测来筛选和验证神经退行性疾病生物标志物候选物的可行性。
使用探索性抗体微阵列和确证性配体结合检测分析来自阿尔茨海默病、帕金森病、多发性硬化症患者及健康对照的脑脊液（CSF）和血浆样本。
筛选抗体微阵列鉴定出神经退行性疾病患者与健康对照之间差异表达的蛋白质，包括分化簇14（CD14）、骨桥蛋白和血管内皮生长因子165b。定量配体结合检测证实，阿尔茨海默病患者脑脊液中CD14水平升高（=0.0177），而帕金森病患者脑脊液中骨桥蛋白水平升高（=0.0346）。
本研究证明了结合探索性蛋白质组学方法和定量配体结合检测来鉴定神经退行性疾病生物标志物候选物的潜在效用。为进一步验证和扩展这些发现，应使用特征明确的样本进行大规模分析。
