Exploration of novel biomarkers for neurodegenerative diseases using proteomic analysis and ligand-binding assays

Abstract

Neurodegenerative diseases are a major cause of morbidity and mortality world-wide, 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 Alzheimers disease, Parkinsons disease, and multiple sclerosis and healthy controls. The screening antibody microarray identified differentially expressed proteins between patients with neurodegenerative diseases and healthy controls. Quantitative ligand-binding assays confirmed that cluster of differentiation 14 (CD14) levels were elevated in CSF of patients with Alzheimers disease, whereas osteopontin levels were increased in CSF of patients with Parkinsons disease. The current study demonstrated the utility of combining an exploratory proteomic approach and quantitative ligandbinding 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.