Insulin resistance and Alzheimer’s disease: the role of defective insulin signaling and inflammation

Introduction Alzheimer’s disease (AD) is the most common form of dementia in the elderly, accounting for 60–80% of cases. The present study was to explore the role of insulin resistance and inflammatory processes in AD patients and to assess the effect of an insulin sensitizer (pioglitazone) on cognition and plasma levels of the amyloid beta derivative. Also, the study aimed to verify experimentally the effect of pioglitazone on the components of brain insulin signaling pathway and inflammatory pathway. Materials and methods We studied the impact of pioglitazone treatment on diabetic AD patients for 6 months with concomitant study of pioglitazone effect on insulin signaling pathway on diabetic AD rats. Results We report that pioglitazone 6 months treated patients has a positive effect on cognitive deficit, improve neurometabolic and decreasing neuroinflammation in diabetic AD patients, and it also was associated with a positive effect on insulin-signaling pathway plus its antioxidant effect on the brain of rats. Conclusion There is a strong association between AD and type 2 diabetes mellitus indicating that they share similar underlying pathophysiological mechanisms. Pioglitazone-treated diabetic AD patients were associated with improvement in cognition.