A lipopolysaccharide mouse model mirrors neuroinflammatory transcriptional signatures of human Alzheimer’s disease, and the Glucagon‐Like Peptide‐1 receptor agonist semaglutide attenuates neuroinflammation in this model

Neuroinflammation is part of the pathophysiology in Alzheimer’s disease (AD). AD neuroimaging studies highlight increased inflammation, while genome wide association studies indicate that many AD‐associated genes are expressed in glial cells. The hormone and neuropeptide Glucagon‐Like Peptide‐1 (GLP‐1) was originally developed for treatment of type 2 diabetes but has equally important effects in weight loss control and provides cardiovascular benefits. The potential for applying a licensed therapeutic option with a well‐established safety profile is currently being investigated in two phase 3a randomized, placebo‐controlled trials with semaglutide in people with early Alzheimer’s disease (evoke/evoke+). Here, we investigate the molecular effects of semaglutide on lipopolysaccharide (LPS) induced hippocampal neuroinflammation in mice and compare the identified pathways with human gene signatures in AD brain tissue.