AD biomarkers including Aβ (40 and 42), Tau (total and pTau), in conjunction with imaging methods, can detect core features of AD and show promise for development of targeted therapeutics (Buckley et al., 2016; Jessen et al., 2014). As noted above, the NIA-AA Research Framework recommends a focus on these markers to enable a more accurate characterization and understanding of neural events that lead to AD-related cognitive and behavioral impairment (Jack et al., 2018). A recent meta-analysis of 51 peer-reviewed studies shows that neural expression of Aβ (40 and 42) and pTau (AT8—Ser181 and Ser199) exhibit strong associations with cognitive decline in the well-validated 3xTg-AD mouse model of AD that expresses human MAPT, APP, and PSEN-1 transgenes (Huber et al., 2018). Taken together with our neuroproteomic data show that alcohol-sensitive protein networks in the PFC and AMY are downstream of the MAPT, APP, and PSEN-1, this provides a strong rationale for evaluating the impact of alcohol intake on NIA-AA biomarkers in 3xTg-AD mice. Here, we evaluated NIA-AA biomarkers in specific brain regions of 3xTg-AD mice as a translational approach to increase understanding of the impact of alcohol drinking on the trajectory of neural pathology in AD.
