Evidently, Tau hyperphosphorylation is a clear sign of the tauopathies and Liu shows that overexpression of GRP78 strengthened the interaction between tau and GSK-3 and caused tau hyperphosphorylation via activating glycogen synthase kinase-3 (GSK-3), a key tau kinase in AD brain. This evidence concerns the gene HSPA5 and tauopathy.