CASP3 and Alzheimer disease: Similarly, metformin decreases p62 in microglia in 3xTg-AD mice [154], inactivates mTOR pathway [155], reducing mTORC1 protein levels [156], and activates AMPK signaling and caspase-3 in P301S mice [155], upregulating the expression of AMPKα1 subunit in 3xTg-AD mice [157].