Since deficits in spatial navigation are pronounced in AD, this finding is important from a translational perspective. The HPC is an initial locus of neurodegeneration in patients affected by Alzheimer’s disease (Braak & Braak, 1991; Whitwell, 2010) with diminished navigational ability presenting as one of the first clinical symptoms (Cherrier, Mendez, & Perryman, 2001; Pai & Jacobs, 2004). Evidence indicates that AD targets specific navigational skills in humans including route learning (e.g., specific orienting skills) and topographic memory or memory for landmarks (e.g., spatial memory and perception) (Lithfous, Dufour, & Despres, 2013). Thus, the present finding that 3xTg-AD mice show diminished spatial learning irrespective of alcohol exposure is consistent with initial development of AD-like pathology in this mouse model and indicative of an AD-like pathology in orienting skills. Importantly, however, our finding that the prior alcohol exposure impaired performance on the MWM memory probe trial in 3xTg-AD mice suggests that nondependent alcohol use may specifically target spatial memory and perception in vulnerable individuals. These results agree with recent evidence from a 30-year longitudinal cohort study in humans showing that long-term
