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American Journal of Alzheimer's Disease and Other Dementias logoLink to American Journal of Alzheimer's Disease and Other Dementias
. 2006 Jun-Jul;21(3):197–208. doi: 10.1177/1533317506289277

Toxic Advanced Glycation End Products (TAGE) Theory in Alzheimer’s Disease

Takashi Sato 1, Noriko Shimogaito 2, Xuegang Wu 3, Seiji Kikuchi 4, Sho-ichi Yamagishi 5, Masayoshi Takeuchi 6
PMCID: PMC10833335  PMID: 16869341

Abstract

Several epidemiological studies have reported moderately increased risks of Alzheimer’s disease (AD) in diabetic patients compared with general population. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress more rapidly. Recent understanding of this process has confirmed that interactions between AGEs and their receptor (RAGE) may play a role in the pathogenesis of diabetic complications and AD. The authors have recently found that glyceraldehyde-derived AGEs (AGE- 2), which is predominantly the structure of toxic AGEs (TAGE), show significant toxicity on cortical neuronal cells and that the neurotoxic effect of diabetic serum is completely blocked by neutralizing antibody against the AGE-2 epitope. Moreover, in human AD brains, AGE-2 is distributed in the cytosol of neurons in the hippocampus and parahippocampal gyrus. These results suggest that TAGE is involved in the pathogenesis of AD as well as other age-related diseases. In this review, the authors discuss the molecular mechanisms of AD, especially focusing on TAGE-RAGE system.

Keywords: advanced glycation end product (AGEs), glyceraldehyde-derived AGEs (AGE-2), toxic AGE (TAGE), receptor for AGEs (RAGE), Alzheimer’s disease (AD), diabetic complications

Full Text

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Contributor Information

Takashi Sato, Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan; Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and the Department of Internal Medicine III, Kurume University School of Medicine, Kurume, Japan.

Noriko Shimogaito, Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan; Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and the Department of Internal Medicine III, Kurume University School of Medicine, Kurume, Japan.

Xuegang Wu, Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan; Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and the Department of Internal Medicine III, Kurume University School of Medicine, Kurume, Japan.

Seiji Kikuchi, Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan; Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and the Department of Internal Medicine III, Kurume University School of Medicine, Kurume, Japan.

Sho-ichi Yamagishi, Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan; Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and the Department of Internal Medicine III, Kurume University School of Medicine, Kurume, Japan.

Masayoshi Takeuchi, Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan; Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and the Department of Internal Medicine III, Kurume University School of Medicine, Kurume, Japan, m-takeuchi@hokuriku-u.ac.jp .

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