For Alzheimer’s disease, causative variants in three key genes–amyloid precursor protein (APP) [17–19], presenilin 1 (PSEN1) [20], and presenilin 2 (PSEN2) [21]–were uncovered in studies of families enriched for early-onset cases. This evidence concerns the gene PSEN1 and early-onset autosomal dominant Alzheimer disease.