MAPT and Alzheimer disease: ALDH2–/– null mice showed progressive cognitive dysfunction from around 3.5–4 months, with AD-like pathological changes, including increased 4-HNE protein adducts in the hippocampus (D’Souza et al., 2015) and cortex (Knopp et al., 2020), Aβ deposition in the brain, tau phosphorylation, increased activated caspase, and defective cAMP-response element binding protein (CREB) signaling (D’Souza et al., 2015; Luo et al., 2016; Knopp et al., 2020).