In the SAMP8 mice of the AD model, metformin reduces the level of tau hyperphosphorylation possibly through inhibiting protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway, calpain 1, GSK3β and cyclin-dependent kinase 5 (Cdk5) activities [120]. Here, MAPT is linked to Alzheimer disease.