Giulio Maria Pasinetti
Icahn School of Medicine USA
Posters-Accepted Abstracts: J Diabetes Metab
Epidemiological evidence supports the observation that subjects with type 2 diabetes (T2D) are at higher risk to develop Alzheimer�??s disease (AD). However, how these conditions are causally linked and how dietary lifestyles interact with these conditions are unknown. Possible mechanisms include shared genetic risk factors, which we investigated in a recent study based on recent genome wide association study (GWAS) findings. We retrieved single nucleotide polymorphisms (SNPs) associated with T2D and AD from large-scale GWAS meta-analysis consortia and tested for overlap among the T2D and AD associated SNPs. We found 927 SNPs associated with both AD and T2D with p-value �?�0.01, an overlap significantly larger than random chance (overlapping p-value of 6.93E�??28). Among these, 395 of the shared GWAS SNPs have the same risk allele for AD and T2D, suggesting common pathogenic mechanisms underlying the development of both AD and T2D. We found that gene annotations from these shared SNPs are significantly enriched for specific KEGG pathways pertaining to immune responses, cell signaling and neuronal plasticity, cellular processes in which abnormalities are known to contribute to both T2D and AD pathogenesis. This suggests that among T2D subjects with common genetic predispositions, dysregulation of these pathogenic pathways could have contributed to the onset of T2D, while simultaneously contributing to the increased risks of these subjects to eventually develop AD. Collectively, our GWAS studies tentatively support the epidemiological observation of disease concordance between T2D and AD. Ongoing studies are investigating whether intensive lifestyle intervention, including exercise and pharmacological treatment, in T2D subjects with genetic predisposition to AD may concurrently reduce T2D phenotypes and attenuate AD onset and progression.
Email: giulio.pasinetti@mssm.edu
