Semaglutide Selectively Improves Metabolic and Cognitive Function in 5xFAD Mice

Alzheimer's disease (AD) and metabolic syndrome frequently co-occur, sharing critical features like insulin resistance, dyslipidemia, and chronic inflammation. This metabolic dysfunction often precedes cognitive decline, suggesting that early intervention could significantly alter AD progression. Current treatments for AD primarily manage symptoms, highlighting an urgent need for therapies that target underlying pathological mechanisms. GLP-1 receptor agonists like semaglutide, known for their metabolic benefits, are being investigated for their potential neuroprotective effects, addressing the critical gap in treating AD's metabolic roots.

Researchers investigated semaglutide's influence on metabolic impairment and AD pathology in a mouse model. Male and female 5xFAD and wild-type (WT) mice were maintained on either regular (RD) or high-fat diets (HFD). Mice were administered semaglutide for 13 weeks. The study assessed body weight, glucose tolerance, cholesterol levels, and adiponectin/leptin balance as metabolic endpoints. AD pathology was evaluated by measuring Aβ40 and Aβ42 levels, GLP-1 receptor expression, and synaptic markers synaptophysin and βIII-tubulin. Cognitive function was assessed via spatial memory tasks, while inflammation was measured by Iba1 and CD68 immunoreactivity in the hippocampus and cortex, and CD36 expression in visceral adipose tissue.