As noted above, glycogen synthase kinase 3 (GSK3) is a serine-threonine kinase that is expressed in the mammalian brain system in two isoforms, GSK3α and GSK3β (Woodgett, 1990). Dysregulated GSK3β activity is associated with several neurological and neuropsychiatric diseases including Alzheimer’s (Cai, Zhao, & Zhao, 2012) and is thought to serve as a molecular link between Aβ and Tau pathology (Llorens-Martin et al., 2014). GSK3β cleaves APP to Aβ and directly phosphorylates Tau at multiple amino acid residues including Ser199/Ser202. Acute and chronic alcohol exposure is known to increase GSK3β phosphorylation (Neasta et al., 2014, 2010, 2011; van der Vaart et al., 2018) but the long-term effects of alcohol use on GSK3 activity and function remain to be elucidated. Results from this study show that a history of alcohol use (1-month post alcohol) is associated with hyperphosphorylation at the GSK3 site on Tau (Ser199/Ser202) in hippocampus (CA1) subregion of 3xTg-AD mouse brain.
