We observed significant alterations of the Akt/Gsκ-3β pathway in 3×Tg-AD mice, at both mild (6-month-old) and severe (12-month-old) stages of pathology, and have also demonstrated for the first time in an in vivo model the ability of um-PEA to prevent such alterations, thus reducing the abnormal phosphorylation of tau. This evidence concerns the gene MAPT and Alzheimer disease.