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.