Defect in Nrf2-Keap-1/ARE-Dependent Redox Signaling in Diabetic Adults in Paving a Path to Alzheimer Disease: A Case–Control Study

Abstract Context: Alzheimer disease (AD) and type 2 diabetes (diabetes mellitus [DM]) prevalence increases with age, and evidence shows a possible link between AD and DM. However, the mechanisms underlying this association have not been fully explained. Here, we underscore oxidative stress and its damaging role in some key regulatory enzymes. Aims: To explore how redox sensing transcription factor Nrf2-keap-1/ARE activation led to the improvement of cognitive function and can be used to provoke neuroprotection and cognitive augmentation. Settings and Design: In this study, a total of 200 study participants (100 study participants with DM and 100 age[<50 years]-matched healthy controls) were recruited from the Department of Medicine, Santosh Hospital, Ghaziabad, India. Materials and Methods: Blood was collected from 100 DM study participants and 100 normal healthy individuals. Blood glucose, glycated hemoglobin (HbA1c), lipid profile, and Nrf2-keap-1/ARE levels were determined along with oxidative stress and circulating amyloid beta in study participants. Statistical Analysis Used: Statistical calculations were performed using SPSS. Student’s “ t ” test and Mann–Whitney “ U ” test were used to conclude the statistical significance. Furthermore, a correlation study was applied. Results: In our study, we found an increase in the level of glucose, lipid profile, and HbA1c in diabetic participants (Group II). Furthermore, oxidative stress and amyloid beta were also increased in group II participants while Nrf2-keap-1/ARE levels were found to be decreased. Collectively, these results suggest that DM may be implicated at different stages of AD through different pathways, and Nrf2-keap-1/ARE is one of them. Conclusions: Elucidation of the underlying pathways that connect these two diseases will be immensely valuable for designing novel drug targets for AD.