Melanotransferrin is produced by senile plaque-associated reactive microglia in Alzheimer's disease

Melanotransferrin (MTf), also known as p97, has been localized in capillary endothelial cells of human brain. In Alzheimer's-diseased (AD) brain tissu es, reactive microglial cells located in senile plaques exhibit elevated le vels of MTf. The localization of the p97 protein may reflect its site of sy nthesis or could reflect a paracrine site of action. We examined the expres sion of MTf mRNA by in situ hybridization histochemistry using AD and healt hy brain tissues. We also examined normal Liver tissues by immunohistochemi stry and in situ hybridization. In all the brain tissues examined, capillar ies had positive signals for MTf mRNA. In AD tissues, expression of MTf mRN A appeared in reactive microglial cells in the grey matter specifically ass ociated with dense plaques. In liver tissues, immunohistochemistry using an ti-p97 antibody demonstrated that sinusoids were positively stained. In add ition, in situ hybridization histochemistry revealed that hepatocytes had p ositive signals. These results suggest that p97 expression in reactive micr oglial cells are closely related to AD pathology. These results also suppor t the notion that p97, which appears elevated in the cerebral spinal fluid and serum of AD patients, originates in the reactive microglia associated w ith dense senile plaques. Thus, p97 is a unique cellular hallmark of AD and further suggests that metal transport mechanisms play a role in this disea se. (C) 1999 Elsevier Science B.V. All rights reserved.