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.