It was also observed in transfected cells and rat brains that activation of GSK-3β could efficiently induce tau hyperphosphorylation at most of the hyperphosphorylated sites seen in the paired helical filaments (PHFs) isolated from AD brains (Lovestone et al., 1994; Hong et al., 1997; Liu et al., 2005; Cavallini et al., 2013). This evidence concerns the gene MAPT and Alzheimer disease.