Here, the present study revealed that AD mice exhibited pronounced cognitive impairment, neuronal damage, and autophagic lysosomal dysfunction, along with a significant increase in Aβ1–42 and Aβ1–40 levels and accumulation of phosphorylated tau protein; however, all these changes could be improved after TIP60 overexpression, indicating that TIP60 plays a protective role in AD pathology. Here, MAPT is linked to Alzheimer disease.