APP and Alzheimer disease: The cause of AD is largely unknown, though impaired clearance of these aggregates appears to be age-related (Vilchez et al., 2014), and an association with several genetic factors, particularly of early-onset AD, have been identified including inherited mutations in amyloid-beta precursor protein (APP), and presenilin genes (PSEN1 and 2) which are involved in amyloid-beta plaque generation (Giri et al., 2016).