MAPT and tauopathy: In a mouse model of tauopathy, chronic metformin treatment-induced PP2A expression through the AMPK/mTOR pathway reduced tau phosphorylation in the cortex and hippocampus of tau-P301S mice [117]; however, metformin also increased the number of insoluble tau species and the number of inclusions with β-sheet secondary structure in the cortex of P301S mice, and promoted the aggregation of recombinant tau protein in vitro [117].