Affiliations: [a] Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan | [b] Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
Correspondence:
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Corresponding author: Dr. Masayoshi Takeuchi, Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan. Tel.: +81 76 229 6197; Fax: +81 76 229 2781; E-mail: [email protected].
Abstract: Recent clinical evidence has suggested diabetes mellitus as one of the risk factors for the development and progression of Alzheimer's disease (AD). Continuous hyperglycemia is a causative factor for diabetic vascular complications, and it enhances the generation of advanced glycation end-products (AGEs), thereby being involved in the pathogenesis of AD as well. Moreover, there is a growing body of evidence to show that the interaction of glyceraldehyde-derived AGEs (Glycer-AGE), which is a predominant structure of toxic AGEs (TAGE), with a receptor for AGEs elicits oxidative stress generation in numerous types of cells, all of which could contribute to the pathological changes of diabetic vascular complications and AD. Indeed, we have recently found that Glycer-AGE induces apoptotic cell death in cultured cortical neuronal cells. We also found that the neurotoxic effect of diabetic serum on neuronal cells was blocked by a neutralizing antibody raised against the Glycer-AGE epitope. Moreover, in human AD brain, Glycer-AGE is distributed in the cytosol of neurons in the hippocampus. These results suggest that Glycer-AGE is involved in the pathogenesis of AD. In this review, we discuss the pathophysiological role for AGEs in the development and progression of diabetic vascular complications and AD, especially focusing on TAGE.
