Preclinical strategies, such as those reported here, allow collection of new and important data implicating a maladaptive role for alcohol in the neuropathological and behavioral developmental trajectory of AD. The 3xTg-AD mouse, and other models of AD, provide a unique opportunity to investigate how alcohol, and other modifiable risk factors, interact with mechanisms of AD and have potential to lead to synergistic discoveries that span research fields focused on age-dependent and drug-induced neurodegeneration. A potential future direction from these studies is to address mechanistic regulation by specific proteins, brain regions, and/or neural circuits. This could be accomplished by site-specific pharmacological, AAV, and optogenetic strategies. One circuit that might be important to evaluate is the projection from the lateral entorhinal cortex to the CA1 region of the HPC. The CA1 subregion shows intrinsic and circuit heterogeneity that may underlie the involvement of this structure in AD-associated behavioral pathologies (Masurkar, 2018); thus, subregional and circuit analyses have potential to identify specific anatomical substrates of alcohol’s impact on AD. Given the involvement of these brain regions in the onset of AD-like pathology, attenuating
