Fluorescence imaging of homocysteine dynamics: Complementary diagnostic applications in Alzheimer's disease.

With the continue emergence of Alzheimer's disease (AD)-modifying therapies, pinpointing the treatments that offer the greatest benefits to patients is increasingly critical. Complementary diagnostics are powerful tests that can provide crucial biomarker dynamics about the drug usage that can improve treatment outcomes by individualized pharmacotherapy. Herein, we exploited a robust near-infrared fluorescent probe, by attenuating the pre-twisting tendency and the twist intramolecular charge transfer effect, for sensing of Hcy in vitro and in vivo with high quantum yield, excellent selectivity, and remarkable sensitivity. The probe is capable of monitoring endogenous Hcy dynamics in cells, tissues and in vivo with exceptional blood-brain barrier permeability. Specifically, we revealed that Hcy can contribute to the onset and development of AD by facilitating the formation of amyloid-β aggregates, elucidating the intricate relationship between brain Hcy levels and AD progression. Furthermore, we investigated the effect of four licensed drugs on endogenous marker Hcy dynamics in cells and in mice with AD model. Our study provides a valuable molecular probe platform utilizing Hcy as a biomarker for supplementary diagnosis applications.