Likewise, HFD has shown to exacerbate brain pathology and related behavioral impairment in APP/PS1 and 3xTg-AD mouse models of AD (Theriault et al., 2016; Sah et al., 2017; Bracko et al., 2020), reinforcing the relevant crosstalk between metabolic and age-associated brain dysfunction. Here, PSEN1 is linked to Alzheimer disease.