Electrochemical Strategy for Analyzing the Co-evolution of Cu and OH Levels at the Early Stages of Transgenic AD Mice.

As more researchers have acknowledged that the aggregation of amyloid β (Aβ) peptides might only be a pathological phenomenon that appears during the course of Alzheimer's disease (AD), it is therefore of great significance to have a preclinical or an early clinical diagnosis. Cu dyshomeostasis and oxidative stress, such as hydroxyl radical (OH), are found to be associated with peptide aggregations. However, we still do not know how the levels of Cu and OH are altered in the brain before massive Aβ plaques appear. Herein, we demonstrated the design and application of a sensitive electrochemical sensor to monitor Cu and OH simultaneously in one system without obvious cross-talk. The electrode was fabricated using black phosphorus-loaded Au (BP-Au) nanoparticles, which were then sequentially linked with DNA1, DNA2-labeled Au (Au-DNA2) nanoparticles, and methylene blue (MB). Cu was first recognized and captured onto the sensor by BP with high selectivity and then produced a reduction current at around -0.01 V. The OH quantification was established on the cleavage of the hybrid structure between DNA1 and BP-Au upon the appearance of OH in the phosphate-buffered saline (PBS), leading to the depletion of the voltammetric response of MB around -0.25 V. Good linear correlations were obtained over concentrations of 0.5-127.5 μM for Cu and 0.5-96.0 μM for OH. Most importantly, the developed sensor was successfully applied to track the variations of the two species in brain tissues from APP/PS1 transgenic AD mice at the early stages before massive Aβ plaques appeared.