Detection of Aβ40 in cerebrospinal fluid and plasma of Alzheimer’s disease patients using photoelectrochemical biosensors

An ultra-sensitive photoelectrochemical (PEC) biosensor for amyloid-beta 40 (Aβ40), a biomarker for Alzheimer’s disease (AD), was developed using g-C₃N₄ modified with gold nanoparticles (Au NPs) to form Au-C₃N₄. This was further combined with TiO₂ to create a tightly bonded TiO₂/Au-C₃N₄ heterojunction, leading to a highly responsive photocatalytic process. Furthermore, the incorporation of noble metal Au NPs not only enhances photocurrent generation but also securely immobilizes the aptamer through Au–S bonds, providing additional surface binding sites. This significantly increases the sensor's capture efficiency. The sensor exhibited excellent performance, featuring a linear detection range from 10−15 to 10−11 g/mL and a remarkably low detection limit (LOD) of 0.33 fg/mL. Moreover, the validation in clinical settings demonstrated the successful detection in real cerebrospinal fluid (CSF) and plasma, from AD patients and non-AD controls. These results strongly suggest that PEC biosensors possess significant potential as cost-effective and highly sensitive tools for detecting ultra-trace substances in human body fluids, which offers promising opportunities for the early screening of high-risk populations for AD.