While familial AD, which accounts for ~1% of AD cases, is likely caused by genetic mutations in APP, PSEN1, and PSEN2 leading to enhanced Aβ production (Thies and Bleiler, 2013), a positive correlation between Aβ levels and APP processing is not evident in sporadic late-onset AD (Shinohara et al., 2014), which represents the bulk of all AD cases. This evidence concerns the gene PSEN2 and Alzheimer disease.