794AKT ACTIVATION AND GSK-3β INACTIVATION IN THE HIPPOCAMPUS ARE ACCELERATED BY DELETING IL-33The present study investigated the role of inteleukin-33 (IL-33), a proinflammatory cytokine, in the activities of Akt and glycogen synthase kinase 3β (GSK-3β). GSK-3β phosphorylates tau protein, causing neurofibrillary tangles (NFT) in the brain of Alzheimer’s disease (AD). The IL-33 protein levels in the hippocampus of 5xFAD mice, an animal model of AD, were significantly higher than the levels for wild-type control mice. Ser473 phosphorylation of Akt and Ser9 phosphorylation of GSK-3β were significantly enhanced in the hippocampus of IL-33-deficient mice as compared with those for wild-type control mice. This indicates that Akt is more activated and GSK-3β is more inactivated by deleting IL-33; i.e., IL-33 inactivates Akt and activates GKS-3β, thereby stimulating tau phosphorylation and NFS formation. Overall, these results raise the possibility that IL-33 may be a factor to accelerate tau phosphorylation in the AD brain.tnishizaki@bioresorganization.comResearch842017IL-33-deficient mouse, Akt, GSK-.Tomoyuki NishizakiTomoyuki Nishizaki