GLP-1 receptor signaling restores water channel organization in reactive brain support cells and helps clear amyloid beta in a mouse model of Alzheimer's disease

Subcutaneous administration of the GLP-1 receptor agonist liraglutide significantly reduced Aβ (1-42) accumulation in the cerebral cortex of an Alzheimer's disease mouse model.

• Glucagon-like peptide-1 receptor (GLP-1R) is predominantly expressed at perivascular sites of astrocytes in the normal mouse cerebral cortex.
• A 20-week treatment with liraglutide improved spatial working memory in the AD mouse model, Appmice.
• Liraglutide treatment for 4 weeks led to the relocalization of aquaporin 4 (AQP4) to the cell surface of reactive astrocytes in Appmice.
• The translocation of phosphorylated AQP4 to the astrocyte cell surface was also confirmed in vitro using a human astrocyte cell line.
• Enhanced GLP-1R signaling may promote Aβ excretion by increasing AQP4-mediated water flow in the brain.

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