Nature 382, 685 - 691 (22 August 1996); doi:10.1038/382685a0

RAGE and amyloid- peptide neurotoxicity in Alzheimer's disease

Shi Du Yan, Xi Chen, Jin Fu, Ming Chen, Huaijie Zhu, Alex Roher^*, Timothy Slattery^†, Lei Zhao^†, Mariko Nagashima^†, John Morser^†, Antonio Migheli^‡, Peter Nawroth^§, David Stern & Ann Marie Schmidt

Departments of Pathology, Surgery, Medicine and Physiology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA ^* Sun Health Research Institute, 10515 Santa Fe Drive, Sun City, Arizona 85372, USA ^† Berlex Biosciences, San Pablo Avenue, Richmond, California 94804, USA ^‡ Clinica Neurologica II, University of Torino, 10126 Torino, Italy ^§ Department of Medicine, University of Heidelberg, Bergheimen Str. 58, 69115 Heidelberg, Germany

Amyloid-beta peptide is central to the pathology of Alzheimer's disease, because it is neurotoxic—directly by inducing oxidant stress, and indirectly by activating microglia. A specific cell-surface acceptor site that could focus its effects on target cells has been postulated but not identified. Here we present evidence that the 'receptor for advanced glycation end products' (RAGE) is such a receptor, and that it mediates effects of the peptide on neurons and microglia. Increased expression of RAGE in Alzheimer's disease brain indicates that it is relevant to the pathogenesis of neuronal dysfunction and death.

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