Anchalee Slaim
Research Mentor(s): Elizabeth Litkowski
Mentor Department: Neurology
Authors: Klaire Schott, Dashoney Bibbie
Session: Session 2 (10:00am – 10:50am)
Presentation Type: Poster 76
Abstract
The cure for Alzheimer’s disease (AD) remains elusive, but evidence increasingly links impaired glucose tolerance to cognitive decline. Recent findings highlight cellular mechanisms of resilience that may counteract the progression of AD, emphasizing the role of specific brain pathways in mitigating these effects. These insights suggest that understanding the relationship between glucose metabolism and cognitive function could provide critical directions for developing therapeutic strategies. This study utilizes a genetically diverse mouse panel with dominant mutations for Alzheimer’s Disease (AD-BXD) to examine the potential for drug repurposing by evaluating the effects of miglitol, an anti-diabetes drug, on cognitive resilience. Half the mice in this study carry mutations known to be associated with AD (“5XFADâ€) while the others do not (“Ntgâ€). A miglitol-infused diet is administered alongside a control “chow†diet, with food intake monitored weekly and animal weights tracked monthly in more than 600 mice. Statistical analyses assess the impact of genetic background, sex, genotype (5XFAD vs. Ntg), and diet on cognitive outcomes, aiming to elucidate mechanisms linking glucose metabolism and cognitive decline. The study’s data, focusing on strains observed to be susceptible to cognitive decline, finds that the effect of miglitol on weight and glucose metabolism differs significantly by sex, genotype, and strain. These findings underscore miglitol’s potential to influence metabolic stability and weight regulation, factors crucial not only for managing diabetes-related weight loss but potentially for addressing cognitive decline in AD models. By further exploring miglitol’s impact on both metabolic and cognitive pathways, the study offers key insights into its potential as a repurposed therapeutic candidate for Alzheimer’s disease, warranting further investigation in subsequent studies.
