The scientific premise of this work was based primarily on our prior analysis of the neuroproteome that revealed a striking, and unanticipated, major association between alcohol and AD pathology in C57BL/6J mice (Agoglia & Hodge, 2017; Salling et al., 2016). A newly conducted bioinformatics analysis of those data identified three primary mechanisms of AD (MAPT, PSEN-1, and APP proteins) as the statistically most likely upstream modulators of alcohol-sensitive protein networks in the PFC and amygdala. Based on this predicted relationship, we sought to evaluate the impact of voluntary nondependent alcohol drinking on AD-like neural and behavioral pathologies in the 3xTg-AD mouse model of AD, which expresses human MAPT, PSEN-1, and APP transgenes (Oddo, Caccamo, Shepherd, et al., 2003).
