Age-related Diseases: Key Role of Insulin Resistance for the Association Between Type II Diabetes and Alzheimer’s Disease

Abstract

Background: Alzheimer’s disease (AD) and Type 2 diabetes mellitus (T2DM) present many relationships. Insulin resistance (IR) plays a key role in neuronal degeneration and death. Reduced energy makes neurons more sensible to oxidation causing mitochondrial damages. Moreover AD brain has lower insulin utilization, reduced expression of its receptors and of IGF 1 and 2, all necessary for neuronal survival and learning and memory processes. Hyperinsulinemia is correlated with increase of hyerphosphorilated tau-protein. SHIP2, a phosphatase, is an antagonist of PI3K. Since the PI3K plays a key role in the biological effects of insulin, its attenuation could be associated with IR in T2DM. Methods: We have conducted a case-control study evaluating the association of three SNPs of SHIP2 in T2DM and AD patients and old and young subjects. SNPs study has been developed by ARMS PCR that make it possible to detect a single SNP thanks to the terminal 3’-nucleotide of one of the primers that anneal with target mutation. Results: Significant differences were observed for one functional SNP between AD patients and young subjects, old and young subjects but not AD patients and old subjects. Conclusions: Our preliminary results seem to suggest a putative correlation between this SNP and aging thus strengthening the hypothesis of a close relationship among AD and diabetes. In fact, to verify this relationship we are collecting blood from T2DM patients. Moreover we will collect AD samples because to confirm these results a bigger cohort needs.