A nanowire-based fluorescent sensor for detecting hydrogen peroxide (H2O2) dyshomeostasis in cell body and synapse of Alzheimer's disease (AD) cell model.

Revealing the levels of hydrogen peroxide (H2O2) in neuron's cell body and synapse with high spatial resolution is very important not only for clarifying the pathways between the fluctuation of H2O2 and neurotoxicity of amyloid-β oligomers (AβOs), but also for further understanding the pathogenesis of Alzheimer's disease (AD). Herein, a single nanowire-based H2O2 fluorescent sensor has been designed and developed by covalently modifying H2O2-responsive molecules onto the surface of silicon nanowires (SiNWs). The sensor features high spatial resolution, excellent selectivity and high sensitivity. By positioning SiNW sensors into both cellular compartments, respectively, the AβOs-induced alterations of H2O2 levels in cell body and synapse of neurons are detected. It is found that H2O2 levels in cell body and synapse are gradually elevated with prolonging AβOs exposure. Moreover, the elevation of H2O2 in synapse occurs prior to the increase in cell body. It is demonstrated that the clathrin-mediated endocytosis serves as a prime pathway mode for transporting exogenous AβOs into the cells, and plays a critical role in preferentially elevating H2O2 levels in synapse. The method developed in this work for monitoring H2O2 with high spatial resolution will be beneficial for exploring the critical role of H2O2 in AD pathogenesis.