APP and familial Alzheimer disease: Alzheimer’s disease is the most common age-related neurodegenerative disease and cause of dementia, estimated to affect close to 50 million people in 2015 worldwide, with cases predicted to almost double every 20 years.1 Autosomal dominant mutations in the Amyloid Precursor Protein (APP) gene or genes encoding the APP proteolytic enzymes Presenilins 1 and 2 (PSEN1, PSEN2) are causative of early-onset familial Alzheimer’s disease.