Insulin signaling, glucose metabolism and mitochondria: Major players in Alzheimer's disease and diabetes interrelation

Many epidemiological studies have shown that diabetes, particularly type 2 diabetes, significantly increases the risk to develop Alzheimer's disease. Both diseases share several common abnormalities including impaired glucose metabolism, increased oxidative stress, insulin resistance and deposition of amyloidogenic proteins. It has been suggested that these two diseases disrupt common cellular and molecular pathways and each disease potentiates the progression of the other. This review discusses clinical and biochemical features shared by Alzheimer's disease and diabetes, giving special attention to the involvement of insulin signaling, glucose metabolism and mitochondria. Understanding the key mechanisms underlying this deleterious interaction may provide opportunities for the design of effective therapeutic strategies.