With a complex genetic etiology and a high heritability, estimated ranging from 60 to 80%2, AD is usually divided into two subgroups of diseases: the familial early-onset AD, caused by mutations in single genes including APP, PSEN1, and PSEN2, and the late-onset AD (LOAD), influenced by multiple common variants with low effect sizes3. The gene discussed is PSEN1; the disease is Alzheimer disease.