APP and Alzheimer disease: The majority of AD appears to be sporadic, with patients who exhibit Late-Onset AD (LOAD), defined as AD with an onset later than 65 years [15], while a small percentage of all AD cases are linked to rare and highly penetrant mutations in one of three principal genes: amyloid precursor protein (APP) [16,17,18,19], presenilin 1 (PSEN1) [20,21], and presenilin 2 (PSEN2) [22,23].