Iron and ferroptosis in the pathogenesis of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is an incurable dementia, with major risk factors being age and the APOE-ε4 allele. AD has a hallmark neuropathology of neuronal death, lipid peroxidation damage, extracellular Aε amyloid and intracellular tau deposition. There is also marked dysregulation of metal homeostasis, with iron elevation reported in cortex (AD) in tandem with the proteinopathies. The major proteins implicated in AD have been found to function in brain iron regulatory system that fails in aging. The amyloid protein precursor, like ceruloplasmin, facilitates the export of iron from cells by stabilizing cell surface ferroportin. Tau impacts on iron export by trafficking APP to the cell surface..