Advances of amyloid β and tau protein detection in Alzheimer's disease: The role of electrochemical biosensors

Alzheimer's disease (AD) is a progressive neurological disorder characterized by the abnormal accumulation of amyloid beta (Aβ) plaques in the extracellular space of the cerebral cortex and hippocampus and tau protein tangles in the cytoplasm of neurons, particularly in the hippocampus and cerebral cortex. Detection of these biomarkers at trace level, before symptoms appear, could enable timely intervention and effective disease management. Electrochemical biosensors with their high sensitivity, low cost, portability, and potential for real-time monitoring offer a transformative approach to AD diagnosis, including Aβ and tau proteins quantification. In this study, we summarize the role of electrode architecture and advanced nanomaterials such as carbon nanostructures, metal nanoparticles, 2D materials, molecularly engineered composites, and conductive polymers, in enhancing electrochemical sensor performance. The principles of various electrochemical techniques, including voltammetry, impedance spectroscopy, and field-effect transistor-based sensing, are also reviewed, along with their applications in detecting AD biomarkers in various biological fluids. Challenges related to reproducibility, stability, and clinical translation are highlighted, and insights are provided on integrating biosensors into microfluidic and wearable systems for point-of-care testing, as well as employing AI approaches for advanced data analysis and diagnostic accuracy.