ALDH2 and Alzheimer disease: In ALDH2–/– null mice (D’Souza et al., 2015; Knopp et al., 2020; Mehder et al., 2021) and ALDH2*2 OE Tg mice (Ohsawa et al., 2008), 4-HNE in the brain is found to be increased early and prior to AD-like symptoms (Figures 1A, B).