Bioanalytical Considerations for Biomarkers of Parkinson's Disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by damage to dopaminergic cells. Early detection of PD is challenging due to the late appearance of clinical symptoms. Therefore, reliable biomarkers are needed to help identify subjects at risk and allow for early intervention, as well as for better monitoring of disease progression and response to therapy. α-Synuclein (α-syn) has emerged as a potential biomarker for PD, along with other biomarkers such as cytokines, amyloid β42, tau protein, and neurofilament light chain. Despite the abundance of biomarker discovery research, comparative studies and biomarker validation have been difficult due to the lack of large longitudinal studies and the corresponding bioanalytical challenges, which limit accurate biomarker measurements and identification. Key bioanalytical challenges in biomarker identification include the need for very sensitive assays with low limits of detection and quantitation, low sample volumes, potential matrix effects, significant amounts of pre-analytical sample processing, and the need to avoid interpretive bias. Various bioanalytical platforms, such as ELISA, MSD, Luminex, Simoa, and mass spectrometry, are used for protein quantification, each with their own advantages and limitations. An α-synuclein seed amplification assay (αSyn-SAA) has shown promise in detecting α-syn aggregates, but standardization and optimization are necessary. Overall, the identification of robust biomarkers for PD requires collaboration, standardization, and the development of sensitive and specific assays.