Exploring the Impact of Semaglutide on Cognitive Function and Anxiety-Related Behaviors in a Murine Model of Alzheimer’s Disease

Background: Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by progressive cognitive decline and behavioral disturbances, with an increasing incidence as the global population ages. This study investigates the effects of semaglutide (SEM), a glucagon-like peptide-1 analog, on cognitive function and anxiety-like behavior in a transgenic murine model of AD. Methods: 20 mice were randomly distributed into the following groups (n = 5): (WT + VEH) group: C57BL/6J + saline, (WT + SEM) group: C57BL/6J + semaglutide, (AD + VEH) group: AD + saline, (AD + SEM) group: AD + semaglutide. The animals underwent a four-week treatment, during which we monitored blood glucose levels, body weight, and responses in an open field test, novel object recognition test, social chamber test, and 0-maze test. Results: Post-treatment, SEM significantly reduced blood glucose levels in AD mice, aligning them with those of wild-type controls. Cognitive assessments indicated an improvement in the investigation index for SEM-treated mice compared to those receiving a vehicle, suggesting cognitive benefits. Although SEM did not significantly enhance motor and exploratory activities, it displayed a potential anxiolytic effect, particularly evident in the combined anxiety index, with notable differences observed before and after treatment in the AD group. Conclusions: The findings of this pilot study suggest that SEM may play a dual role in managing AD by improving glycemic control and potentially enhancing cognitive function. As the landscape of AD treatment evolves, the comprehensive approach of utilizing SEM could pave the way for innovative interventions targeting the complex interplay of metabolic and cognitive dysfunctions in this challenging neurodegenerative disorder.