Results from the present preclinical study indicate that a history of alcohol exposure is associated with a biomarker profile that is consistent with alcohol-induced expression of Alzheimer’s disease in 3xTg-AD mice. First, alcohol exposure resulted in an increase in the Aβ (42/40) ratio in the LEC and PFC (Fig. 6A and B). Aβ (42) is the toxic form of Aβ and is upregulated in postmortem brains of AD patients. This results in an A+ categorization and is indicative of presence on the AD continuum (Table 2). Second, we observed an increase in total Tau protein expression in the LEC, mPFC and AMY. An increase in total Tau protein is indicative of neurodegeneration or neuronal injury and represents an N+ categorization. These data indicate that alcohol use was associated with an A + T(N)+ combination, which indicates Alzheimer’s and concomitant non-Alzheimer’s pathology in the LEC, which is an initial anatomical target of AD pathology (Table 2). In addition, immunohistochemistry was used to measure pTau expression. Qualitative results showed a prominent upregulation of pTau (Ser199/202) in the hippocampus (CA1) of alcohol-exposed 3xTg-AD
