[Pathological interaction between diabetes mellitus and Alzheimer's disease]

The incidence of dementia and diabetes mellitus is increasing at an alarming rate, and has become a major public health concern all over the world. Recent epidemiological studies suggest that the risk of Alzheimer's disease is increased in individuals with diabetes mellitus, although the underlying mechanisms remain largely unknown. To analyze underlying mechanisms linking Alzheimer's disease and diabetes mellitus, we established unique animal models that show pathological manifestations of both diseases. Our findings suggest that impaired brain insulin signaling and cerebrovascular changes could be potential underlying mechanisms for this relationship. On the other hand, interestingly, Alzheimer's amyloid pathology aggravated diabetes mellitus in these mouse models, suggesting the presence of mutual interaction between these diseases. In addition, we also found that plasma Abeta levels rapidly and strikingly increased after glucose loading in Alzheimer's disease mouse models, which could be a novel diagnostic marker of Alzheimer's disease. The current review summarizes the results of our recent studies on the pathological relationship between these diseases, which could provide novel insights into this intensely debated association.