The amyloid precursor protein is so named, because a proteolytic fragment of it was found associated with a neuropathic disorder now known as Alzheimer's disease. This fragment, Aβ, along with tau makes up the plaques and tangles that are the hallmark of AD. Iron (and other first-row transition metals) is found associated with these proteinaceous deposits. Much research has focused on the relationship of the plaques and iron to the etiology of the disease. This commentary asks another question, one only more recently addressed namely, what is the physiologic function of the amyloid precursor protein (APP) and of its secretase-generated soluble species? Overall, the data make clear that APP and its products have neurotrophic functions and some data indicate one of these may be to modulate the trafficking of iron in the brain.
Keywords: APP-like proteins; Alzheimer’s disease; Amyloid precursor protein; Cell surface protein; Ferroportin; Hephaestin; Iron efflux; Iron metabolism; Membrane transport; Metal binding; Metal transport.