APP and Alzheimer disease: Recently, next generation sequencing has led to enormous progress in AD genetics, with the discovery of 2 rare significant risk factors, mapping to TREM2 (p.R47H) and PLD3 (p.V232M), and a very rare protective variant in APP (p.A637T) (Cruchaga et al., 2013, Guerreiro et al., 2013, Jonsson et al., 2012).