Liraglutide improves cognitive function by reducing amyloid-beta peptide accumulation and inhibiting inflammation in 5×FAD mice

Abstract The glucagon-like peptide-1 analog, liraglutide, has been shown to be effective in Alzheimer’s disease (AD); however, the underlying mechanism remains unknown. In this study, we evaluated the effects of liraglutide (25 nmol/day for 8 weeks) on the cognitive ability of 12-month-old 5× familial Alzheimer’s disease (FAD) mice. The spatial cognitive ability was improved in 5×FAD mice after administration of liraglutide, associated with an increased number of pyramidal cells in the cortex and hippocampus. Liraglutide also alleviated the ultrastructural changes in chemical synapses and pyramidal cells and reduced local and universal inflammation in AD mice. Furthermore, liraglutide reduced the expression of amyloid β protein through the regulation of nuclear factor kappa B/beta-secretase 1 pathways in AD mice. The potential of liraglutide to improve the cognitive function in AD animals offers an effective pharmacological approach for treating neurodegenerative diseases.