APP and Alzheimer disease: They also found that HupA induced a significant increase in the phosphorylation levels of both GSK-3α and GSK-3β proteins in APP/PS1 mouse brain and APPsw-overexpressing cells, while activation of both GSK-3α and GSK-3β through their autophosphorylation has been implicated in AD pathogenesis (Caricasole et al., 2004).