APP and Alzheimer disease: Tarantini et al. (2018) fed Nrf2 knockout mice a HFD (60% fat) for 5 months, with Nrf2 deficiency significantly increasing HFD-induced brain inflammation, oxidative stress, synaptic disruption and BBB permeability, as well as raising levels of amyloid precursor protein (APP) gene expression, the proteolysis of which produces Aβ. The authors concluded that Nrf2 dysfunction exacerbates the obesity-induced adverse effects in the brain and plays a role in vascular cognitive impairment and AD (Tarantini et al., 2018).