APP and familial Alzheimer disease: AD consists of two forms; familial or early-onset AD (FAD), which constitutes less than 5% of all AD cases and is normally diagnosed prior to the age of 65 years, with clear genetic risk through inherited mutations in three main genes: amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2; Selkoe, 1996).