REACTIVE MICROGLIA SPECIFICALLY ASSOCIATED WITH AMYLOID PLAQUES IN ALZHEIMERS-DISEASE BRAIN-TISSUE EXPRESS MELANOTRANSFERRIN

Several investigations have implicated the involvement of metals in ne uropathologies. In particular, the disruption of iron metabolism and i ron transport molecules have been demonstrated in Alzheimer's disease (AD). We have identified a novel pathway of iron uptake into mammalian cells involving melanotransferrin, or p97, which is independent of th e transferrin receptor. Here we investigated whether there is a possib le link between this molecule and the pathology of AD. The distributio ns of melanotransferrin, transferrin and the transferrin receptor were studied immunohistochemically in brain tissues from AD cases. In brai n tissues from AD, melanotransferrin and the transferrin receptor were highly localized to capillary endothelium, while transferrin itself w as mainly localized to glial cells. In brain tissue derived from AD pa tients, melanotransferrin was additionally detected in a subset of rea ctive microglia associated with senile plaques. Our demonstration that melanotransferrin mediates iron uptake through a pathway independent of the transferrin receptor indicates that this mechanism may have a r ole in AD.