RAGE AND AMYLOID-BETA PEPTIDE NEUROTOXICITY IN ALZHEIMERS-DISEASE

Amyloid-beta peptide is central to the pathology of Alzheimer's diseas e, because it is neurotoxic-directly by inducing oxidant stress, and i ndirectly by activating microglia. A specific cell-surface acceptor si te that could focus its effects on target cells has been postulated bu t not identified. Here we present evidence that the receptor for advan ced glycation end products' (RAGE) is such a receptor, and that it med iates effects of the peptide on neurons and microglia. increased expre ssion of RAGE in Alzheimer's disease brain indicates that it is releva nt to the pathogenesis of neuronal dysfunction and death.