Amyloid and tau pathology are hallmarks of Alzheimer’s disease but do not fully explain selective neuronal vulnerability. Iron dysregulation has emerged as a critical contributor, as iron accumulation is consistently observed in vulnerable brain regions and is linked to neuronal death. The limited and variable success of bulk iron-targeting approaches underscores the need to resolve iron’s oxidation states and cell type–specific functions in disease.
To address this challenge, I developed the first DNAzyme-based fluorescent probes capable of distinguishing Fe(II) from Fe(III) in living cells and brain tissue Science Advances, 2023). These sensors enabled cellular-resolution imaging of iron oxidation states in diseased samples, revealing localized redox imbalance near amyloid plaques. These molecular innovations open a window into redox imbalance at the level of individual neurons and glia, providing the first oxidation state–specific evidence that iron dysregulation corelates to cognitive aging (Nature Aging, 2025) and disease mechanisms.
Building on this foundation, my independent program will construct an atlas of iron redox states in the brain, test whether imbalance accelerates tau aggregation and spread, and identify the cell types and pathways most at risk. The long-term goal is to move from correlative measures of iron burden to mechanism-guided, stage-specific biomarkers and interventions that can be evaluated in preclinical and clinical studies.