Competitive-SELEX discovery of DNA aptamers selective for neurofilament light chain in human plasma

Neurofilament light chain (NfL) is a blood-based biomarker closely associated with neurodegeneration and the progression of Alzheimer's disease. Here, we report the identification of novel single-stranded DNA aptamers that specifically recognise NfL with high affinity. Using a competitive SELEX strategy incorporating NfL, we enriched aptamer candidates that selectively bind the clinically relevant region of NfL. Two lead aptamers, MN711 and MN734, displayed nanomolar dissociation constants of 11 nM and 8.1 nM, respectively, comparable to those of widely used anti-NfL antibodies. Circular dichroism spectroscopy confirmed parallel G-quadruplex structures, and both aptamers showed minimal off-target binding to amyloid β40, amyloid β42, or phosphorylated tau181. Importantly, MN711 retained concentration-dependent binding to NfL spiked into human plasma. These aptamers provide promising ligand candidates for NfL biosensing platforms and blood-based diagnostic devices for neurodegenerative diseases.