APP and Alzheimer disease: Genetic analysis of AD patients established three causative genes (APP, PSEN1 and PSEN2) and a high-risk allele (ApoE ε4) [5,6], whereas genome-wide association studies led to the discovery of more than 20 low-risk genetic loci [7,8,9], and more recently, high-throughput sequencing identified rare, medium-risk genes, such as TREM2 [10] and UNC5C [11].