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

Abstract

BACKGROUND: Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive memory decline. The increasing prevalence of AD has attracted considerable attention globally. The glucagon-like peptide-1 analog, liraglutide, a drug widely used in the treatment of type 2 diabetes, has shown promising neuroprotective effects in AD, including enhancing neuronal survival, reducing amyloid beta protein accumulation, improving synaptic plasticity, and reducing tau protein hyperphosphorylation. However, its potential impact on cognitive function remains unclear. METHODS: We evaluated the effects of liraglutide (25 nmol/day for 8 weeks) on the cognitive ability of 12-month-old 5 × familial AD (FAD) mice. The Morris water maze test was used to evaluate the spatial learning ability of mice. Histological evaluations were performed by Nissl staining and transmission electron microscopy. Neuroinflammation was detected by double immunofluorescence staining and enzyme-linked immunosorbent assay. Protein expression in the cortex and hippocampus was detected by immunohistochemistry and Western blotting. RESULTS: The spatial cognitive ability improved in 5 × FAD mice after liraglutide administration and was associated with an increased number of pyramidal cells in the cortex and hippocampus. Liraglutide also alleviated ultrastructural changes in the chemical synapses and reduced both local and systemic inflammation in AD mice. Furthermore, liraglutide reduced amyloid β protein expression, which may be associated with the regulation of nuclear factor kappa B/beta-secretase 1 pathways in AD mice. CONCLUSIONS: The potential of liraglutide to improve cognitive function in AD mice offers an effective pharmacological approach for treating neurodegenerative diseases.