Based on results of the URA that identified MAPT, APP, and PSEN-1 as regulators of alcohol’s impact on the neuroproteome, the present set of studies were designed to utilize the “humanized” triple-transgenic mouse model of AD (3xTg-AD mice). This mouse model carries a knock-in mutation of three human genes detected in our analysis: presenilin (PSEN-1M146V), amyloid beta precursor protein (APPSwe), and microtubule-associated protein Tau (TauP30IL), expressed on a hybrid C7BL/6;129X1/SvJ;129S1/Sv genetic background (Oddo, Caccamo, Shepherd, et al., 2003). The 3xTg-AD mouse line is a well-validated animal model of AD that develops rapid age-dependent and progressive AD-like neuropathology including Aβ deposits and elevated Tau (Billings, Oddo, Green, McGaugh, & LaFerla, 2005; Oddo, Caccamo, Kitazawa, Tseng, & LaFerla, 2003; Oddo et al., 2006). These neuropathies are associated with behavioral deficits including cognitive decline and altered emotional processing that are characteristic of AD (Filali et al., 2012; Pietropaolo, Feldon, & Yee, 2014; Romano et al., 2014; Webster et al., 2014). A meta-analysis of 51 studies using the 3xTg-AD mice found that Tau and Aβ (40 and 42) expression showed a strong association with impaired cognitive function (Huber, Yee, May, Dhanala, & Mitchell, 2018).
