Neelima Chauhan, Francesca Davis, Chun Xiao and Balwantsinh Chauhan
20 South Damen Avenue, Chicago, IL 60612; USA
Alzheimer’s disease (AD) is a global health crisis and may escalate if effective treatments are not discovered. Emerging evidence indicates a link between diabetes and AD. Insulin acts as a neuroprotective factor and hence used as a therapy for AD. However, Insulin produces hypoglycemia and elevates Aß due to its competition with insulin degrading enzyme (IDE) that degrades both insulin and Aß. Therefore, approaches other than insulin that prevent hypoglycemic episodes while reducing hyperglycemia are emerging. One such approach is the use of incretins-a group of gut hormones-such as Glucagon-like peptide 1 (GLP1), that stimulates insulin release during hyperglycemia, while simultaneously preventing hypoglycemia and maintaining euglycemia. GLP1 is neuroprotective acting via GLP1 receptors (GLP1R) expressed on neurons. However, long-term systemic use of GLP1 analogues causes pancreatitis. In order to circumvent systemic adversities, we used intranasal route of delivery of GLP1 conjugated with wheat germ agglutinin (WGA) carrier protein for efficient nose-to brain penetration. Current study demonstrated that intranasal WGA-GLP1 reduced neuroinflammation, prevented neuronal loss and preserved synaptic degeneration in 5XFAD model of AD. Intranasal WGA-GLP1 has a great therapeutic potential for treating Alzheimer’s disease.