Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced alzheimer disease mouse model

Type 2 diabetes mellitus is a risk factor for Alzheimer's disease (AD). The glucagon-like peptide-1 analog liraglutide, a novel long-lasting incretin hormone, has been used to treat type 2 diabetes mellitus. In addition, liraglutide has been shown to be neurotrophic and neuroprotective. Here, we investigated the effects of liraglutide on amyloid beta protein (A beta)-induced AD in mice and explored its mechanism of action. The results showed that subcutaneous administration of liraglutide (25nmol/day), once daily for 8 weeks, prevented memory impairments in the Y Maze and Morris Water Maze following A beta(1-42) intracerebroventricular injection, and alleviated the ultra-structural changes of pyramidal neurons and chemical synapses in the hippocampal CA1 region. Furthermore, liraglutide reduced A beta(1-42)-induced tau phosphorylation via the protein kinase B and glycogen synthase kinase-3 beta pathways. Thus liraglutide may alleviate cognitive impairment in AD by at least decreasing the phosphorylation of tau. (C) 2016 Elsevier B.V. All rights reserved.