Advanced ultra-sensitive methods for biomarker detection in neurodegenerative diseases

Objective: Neurodegenerative diseases (NDDs), including Alzheimer’s (AD) and Parkinson’s (PD), are progressive disorders characterized by neuronal dysfunction, protein aggregation, neuroinflammation, and synaptic failure. Advances in biomarker discovery, particularly in cerebrospinal fluid (CSF), have transformed early diagnosis and disease monitoring. This study aimed to evaluate and compare the analytical performance of two ultra-sensitive immunoassay platforms for quantifying neurofilament light chain (NfL) in CSF and plasma K2-EDTA. Materials and Methods: Two platforms, chemiluminescence immunoassay (CLIA; Lumipulse G, Fujirebio) and single molecule array (SIMOA; Quanterix), were evaluated for NfL measurement. Analytical parameters, including dynamic range, sensitivity, reproducibility, and method agreement, were assessed using correlation analysis and Passing-Bablok regression. Results: SIMOA showed superior sensitivity and a wider dynamic range compared to CLIA in both CSF (77–83,319 ng/L) and plasma (4.5–191.8 ng/L). Strong correlations were observed between platforms (CSF Spearman’s rho = 0.98; plasma rho = 0.9339). Passing-Bablok regression revealed a proportional negative bias in CSF (slope = 0.90) and a constant positive bias in plasma (intercept = 1.33). These findings confirm the reliability of both platforms across biological fluids, though method-specific calibration is necessary. Discussion: Both platforms enabled highly sensitive and reproducible NfL quantification in CSF and plasma. The strong correlations support their robustness, but systematic biases highlight the need for platform-specific reference ranges and consideration of matrix effects. Comparative analysis across two biologically relevant fluids enhances the translational value of these assays for early diagnosis and monitoring of neurodegenerative diseases, supporting broader clinical implementation.