This study investigates the role of iron accumulation in the oxidative damage associated with Alzheimer's disease (AD). The authors used a modified histochemical technique to detect redox-active iron in the brains of AD patients, focusing on senile plaques and neurofibrillary tangles, the key pathological lesions of AD. They found that these lesions are associated with iron(III), which can participate in in situ oxidation and catalyze H₂O₂-dependent oxidation. Iron could be removed using deferoxamine but could be reassociated with the lesions using exchangeable sources of iron. The iron-binding site was found to depend on available histidine residues and protein conformation. These findings suggest that iron accumulation is a significant contributor to the oxidative damage in AD.This study investigates the role of iron accumulation in the oxidative damage associated with Alzheimer's disease (AD). The authors used a modified histochemical technique to detect redox-active iron in the brains of AD patients, focusing on senile plaques and neurofibrillary tangles, the key pathological lesions of AD. They found that these lesions are associated with iron(III), which can participate in in situ oxidation and catalyze H₂O₂-dependent oxidation. Iron could be removed using deferoxamine but could be reassociated with the lesions using exchangeable sources of iron. The iron-binding site was found to depend on available histidine residues and protein conformation. These findings suggest that iron accumulation is a significant contributor to the oxidative damage in AD.