Transgenic models that express APP or PSEN-1 mutations may be utilized for identifying alcohol-mediated changes in brain and behavioral function linked specifically to amyloid pathology. As discussed above, APP is cleaved by γ-secretase (e.g., PSEN-1) to form Aβ peptides (Aβ40 and Aβ42), which contribute to amyloid plaques in AD. Transgenic mouse lines that express APP or PS1 mutations, or their combination, exhibit amyloid pathology such as elevated Aβ42/Aβ40 ratio and presence of plaques. A recent study showed that APP23/PS45 mice that express a double (APP/PSEN1) transgenic mutation exhibit increased APP, β-secretase 1, Aβ40, and Aβ42 following alcohol binge-like exposure with concomitant deficits in spatial learning and memory (Huang et al., 2018). The widely used 5XFAD mouse line express a total of five human APP and PSEN-1 trans-genes, which results in rapid onset of amyloid plaques throughout the cortex and hippocampus as early as 2 months of age (Oakley et al., 2006) and could, therefore, be used to assess site-specific amyloid pathology associated with alcohol exposure. The 5XFAD mouse line also shows a deficit in spatial memory (Xiao et al., 2015) suggesting that cognitive decline associated with amyloid pathology can be modeled in APP/PSEN-1 transgenic mouse lines.
