LB-100, an inhibitor of PP2A, could extensively eliminated the effect of fluoxetine on β-catenin, which will result in the down-regulation of Wnt/β-catenin signaling and the neuronal apoptosis, Thus, it could be implied that fluoxetine could specifically activate PP2A to dephosphorylate β-catenin on S33/S37/T41 and GSK3β on Y216 for upregulation of Wnt/β-catenin signaling in 3×Tg AD mice. This evidence concerns the gene GSK3B and Alzheimer disease.