Specifically, our in vivo and in vitro studies showed that nuclear translocation of TFEB decreased in the hippocampus of T2DM mice and in high glucose (HG) cultured HT22 cells, while mTOR-dependent TFEB activation at the post-translational level, as well as neuronal-targeted TFEB overexpression at the transcriptional level, can promote ALP-targeted clearance of AD-related proteins such as Aβ and p-Tau, which ultimately resulted in the alleviation of DE. This evidence concerns the gene MTOR and Alzheimer disease.