Illuminating Fe³⁺ spatiotemporal dynamics in Alzheimer's disease via a lipid-activated ultrasensitive probe

Abnormal iron metabolism is recognized as one of the pathological factors underlying Alzheimer's disease (AD). However, the precise relationship between Fe³⁺ and the AD progression remains incompletely understood. In this study, we introduce a lipid-activated probe, NRA, specifically designed for the detection of Fe³⁺. NRA exhibits excellent stability, high selectivity for Fe³⁺, and a distinct lipid-targeting capability. By using this probe, in the AD cell models successfully induced and constructed with various stimulants, it has been demonstrated that the level of Fe³⁺ gradually increases in AD. More importantly, in vivo studies have shown a significant correlation between Fe³⁺ and amyloid plaques, and its distribution is spatially correlated with lipid enriched regions. Fluorescence lifetime imaging microscopy (FLIM) further revealed that Fe³⁺ exhibits unique distribution patterns across different stages of AD and various brain regions, suggesting an important role in AD pathogenesis. Collectively, these findings provide a novel perspective on the role of Fe³⁺ in AD pathogenesis.