Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice

A number of studies suggest an association between Alzheimer's disease (AD) and diabetes: AD patients show impaired insulin function, whereas cognitive deficits and increased risk of developing AD occur in diabetic patients. The reasons for the increased risk are not known. Recent studies of disturbances in the insulin-signaling pathway have revealed new perspectives on the links between AD and Type 1 diabetes with a particular focus on glycogen synthase-kinase-3 (GSK3). We have therefore characterized a mouse model of combined insulin-deficient diabetes and AD and find that diabetes exaggerated defects in the brain of APP transgenic mice. Mice with combined APP overexpression and diabetes showed a decreased insulin receptor activity and an increased GSK3β activity. Concomitantly, tau phosphorylation and number of Aβ plaques, the two pathologic hallmarks of AD, were increased in the brain of diabetic-APP transgenic mice. Our results indicate that the pathologic features of AD are exaggerated in the brain of APP transgenic mice that have concurrent insulin-deficient diabetes, and underscore a possible mechanism of brain dysfunction common to AD and diabetes.