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International Journal of Alzheimer’s Disease
Volume 2012 (2012), Article ID 734956, 13 pages
Review Article

The Complexity of Sporadic Alzheimer’s Disease Pathogenesis: The Role of RAGE as Therapeutic Target to Promote Neuroprotection by Inhibiting Neurovascular Dysfunction

1Laboratoire des Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (NICN), CNRS, UMR6184, Boulevard Pierre Dramard, 13344 Marseille, France
2Department of Medicine 1, University Hospital of Heidelberg, 69120 Heidelberg, Germany

Received 2 November 2011; Accepted 2 December 2011

Academic Editor: Kiminobu Sugaya

Copyright © 2012 Lorena Perrone et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alzheimer's disease (AD) is the most common cause of dementia. Amyloid plaques and neurofibrillary tangles are prominent pathological features of AD. Aging and age-dependent oxidative stress are the major nongenetic risk factors for AD. The beta-amyloid peptide (Aβ), the major component of plaques, and advanced glycation end products (AGEs) are key activators of plaque-associated cellular dysfunction. Aβ and AGEs bind to the receptor for AGEs (RAGE), which transmits the signal from RAGE via redox-sensitive pathways to nuclear factor kappa-B (NF-κB). RAGE-mediated signaling is an important contributor to neurodegeneration in AD. We will summarize the current knowledge and ongoing studies on RAGE function in AD. We will also present evidence for a novel pathway induced by RAGE in AD, which leads to the expression of thioredoxin interacting protein (TXNIP), providing further evidence that pharmacological inhibition of RAGE will promote neuroprotection by blocking neurovascular dysfunction in AD.