Simultaneous Fe 2+ /Fe 3+ imaging shows Fe 3+ over Fe 2+ enrichment in Alzheimer’s disease mouse brain

Visualizing redox-active metal ions, such as Fe 2+ and Fe 3+ ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe 2+ and Fe 3+ simultaneously in living cells with high selectivity and sensitivity has not been reported. Here, we selected and developed DNAzyme-based fluorescent turn-on sensors that are selective for either Fe 2+ or Fe 3+ , revealing a decreased Fe 3+ /Fe 2+ ratio during ferroptosis and an increased Fe 3+ /Fe 2+ ratio in Alzheimer’s disease mouse brain. The elevated Fe 3+ /Fe 2+ ratio was mainly observed in amyloid plaque regions, suggesting a correlation between amyloid plaques and the accumulation of Fe 3+ and/or conversion of Fe 2+ to Fe 3+ . Our sensors can provide deep insights into the biological roles of labile iron redox cycling.