GSK3 is a key member of the Akt/mTOR cell signaling pathway. Given the upregulation of pTau (Ser199/202) immunoreactivity observed in CA1, we predicted that alcohol use would be associated with altered GSK3 phosphorylation in this brain region. However, alcohol exposure was associated with trends for increased GSK3α (Ser21) and decreased GSK3β (Ser9) phosphorylation in CA1. Since GSK3α activity is increased by phosphorylation and GSK3β activity is increased by dephosphorylation, these trends in phosphorylation may have been enough to support increased Tau phosphorylation. Further work is needed to determine if alcohol-induced changes in GSK3 phosphorylation modulate Tau phosphorylation and expression of AD-like pathology.
