Nano-Collision Electrochemistry for Real-Time Monitoring of Amyloid-β Oligomerization and Rapid Screening of Degrading Drugs

Toxic oligomers of amyloid-β (Aβ) are important in the pathology of Alzheimer's disease (AD), and degradation of Aβ oligomers (AβO) in the brain is considered a promising strategy for drug development. However, conventional drug screening techniques face challenges in the rapid and real-time assessment of AβO. Here, we report a simple and reliable nanocollision electrochemical method based on silver nanoparticles (AgNPs) "tagging" that can in situ monitor Aβ oligomerization and screen potential AβO-degrading drugs. The differences in collision signals between AgNPs-Aβ complexes and AgNPs were compared to achieve rapid identification of Aβ complexes with different aggregation degrees. The degradation effect following the addition of AβO-degrading drugs can be quickly evaluated by the recovery of collision frequency (f, number of peaks per unit time), which is effective if f > 0.15. Degradation efficiency was further quantified using current lifetimes (τ, the time required for the current to decay to 1/e of the original), based on the percentage of τ ≤ 10 ms. The practicability of the method was tested using Aβ-degrading protease and several small molecules, confirming the rapid screening of AβO-degrading drugs and offering a novel strategy to accelerate the development of drugs for AD treatment.