PSEN1 and Alzheimer disease: Genetic analyses of AD and control cases have elucidated three causative genes (APP, PSEN1, and PSEN2), high-risk genes (APOE4 and TREM2) and about 100 low-risk genes and loci11-20, However, the molecular mechanisms of these proteins/genes in AD development are not fully understood, often due to the lack of suitable cellular or animal models.