APP and Alzheimer disease: In addition to well-characterized AD susceptibility genes such as APP, PSEN1 and PSEN2 (early-onset familial AD [4]), and APOE (late-onset AD [5, 6]), several additional risk alleles for late-onset AD were identified in genes regulating immunomodulation, including TREM2 [7, 8], phosphoinositide phospholipase Cγ2 (PLCG2) [9] and CD33 [10, 11].