APP and early-onset autosomal dominant Alzheimer disease: Alzheimer’s disease (AD) is a prevalentneurodegenerativedisease that is the leading cause of dementia in the elderly.1 It was first identified over a century ago bythe German neuropsychiatrist, Alois Alzheimer,2 and now has been proven to have a complicated genetic architecture.3 The encoding genes, such as presenilin-1 (PSEN1)and presenilin-2 (PSEN2), which are part of the γ-secretasecomplex, along with the ε4 allele of apolipoprotein E (APOE)and amyloid precursor protein (APP), exhibit a high degree of mutationpenetrance.