Electrochemical and Optical Biosensors for Acetylcholine Monitoring in Neurodegeneration.

Abstract

Acetylcholine (ACh) plays a pivotal role in cognition, learning, memory, and neuronal plasticity, and alterations in cholinergic neurotransmission are closely associated with neurodegenerative disorders, particularly Alzheimer's disease and related dementias. Consequently, the development of analytical tools capable of accurately monitoring ACh has attracted considerable interest in both neuroscience and clinical research. However, the determination of ACh remains challenging because of its low physiological concentrations, rapid enzymatic degradation, and the complexity of biological matrices. This review provides a comprehensive overview of recent advances in electrochemical and optical biosensors developed for ACh detection, with particular emphasis on progress reported between 2020 and 2026. The sensing principles, analytical performance, and technological characteristics of enzymatic and non-enzymatic electrochemical platforms, as well as colorimetric, fluorescent, surface plasmon resonance, and emerging molecular optical sensors, are critically discussed. Particular attention is given to the role of nanomaterials, signal-amplification strategies, miniaturized devices, wearable and implantable platforms, and approaches enabling real-time monitoring. Recent studies demonstrate remarkable improvements in sensitivity and detection limits; however, translation towards clinical applications remains limited by challenges related to selectivity in complex biological samples, biofouling, long-term stability, reproducibility, and the scarcity of validation studies involving authentic patient-derived specimens. Overall, current advances indicate a shift from proof-of-concept sensor development towards application-oriented platforms aimed at continuous neurochemical monitoring and point-of-care analysis. Future progress will depend on achieving robust performance in physiologically relevant environments and establishing clinically validated biosensing strategies for the assessment of cholinergic dysfunction in neurodegenerative diseases.