APP and Alzheimer disease: Mutations in amyloid precursor protein (APP), and in the proteases that generate beta-amyloid from APP, Presenilin-1 (PS1, PSEN1) and Presenilin-2 (PS2, PSEN2) can cause early-onset AD, and apolipoprotein E/E4 (APOE4), a protein implicated in lipid metabolism and inflammation, is a strong genetic risk factor for late-onset AD (Van Cauwenberghe et al., 2016; Kumar K. et al., 2018).