Alzheimer's disease (AD) ranks as a prototypical age-related neurodegenerative disorder. Emerging evidence indicates that disrupted brain iron metabolism and ferroptosis act as critical upstream drivers of AD pathological progression. AD exhibits core hallmarks of ferroptosis, including iron overload, lipid peroxidation, elevated reactive oxygen species, and impaired antioxidant enzyme activity. These abnormalities interact synergistically with amyloid-β plaques and tau pathology. Iron accumulation during aging and damage-associated molecular patterns released concomitantly with ferroptosis drive susceptible microglia toward M1-like polarization, propagate chronic neuroinflammation, and fuel the vicious cycle of AD pathology. Targeting ferroptotic pathways represents a promising strategy to alleviate cognitive impairment in AD. Ferro-aging ranks as a recently identified form of programmed cellular senescence marked by iron dependency, ACSL4 regulation, and lipid peroxidation-driven damage. Although ferro-aging has only been preliminarily validated in aging models, its molecular signatures, regulatory axes, and phenotypic outcomes align remarkably well with the progression of brain aging and AD. It thus emerges as a potentially pivotal hub linking physiological aging to iron-associated pathology in AD. We systematically summarize the physiological regulation of brain iron homeostasis and core ferroptotic pathways disrupted in AD. We further integrate current evidence to explore how ferro-aging may contribute to AD pathogenesis, proposing a mechanistic framework in which: iron dyshomeostasis initiates damage, ferro-aging drives chronic progression, and ferroptosis mediates acute injury. Finally, we review intervention strategies targeting iron-related pathology, providing theoretical insights for understanding the aging-dependent nature of AD and developing novel therapeutic approaches.
