Studies of late onset AD (typically defined as onset age >65 y) have demonstrated the risk of sequence variants such as the common ε4 allele of apolipoprotein E (APOE), rare variation in TREM2 [3–7], and MAPT [8], as well as numerous common variants contributing modest AD risk [9], including single nucleotide polymorphisms (SNPs) in the following loci: CR1, BIN1, INPP5D, MEF2C, CD2AP, ZCWPW1, NME8, EPHA1, CLU, PICALM, MS4A4, CELF1, FERMT2, ABCA7, CD33, CASS4, PTK2B, SORL1, SLC24A4-RIN3, DSG2, and HLA-DRB5/HLA-DRB1 [9,10]. This evidence concerns the gene CASS4 and Alzheimer disease.