PSEN2 and Alzheimer disease: However, genetic variants in four well-established genes for early-onset AD (EOAD), namely, amyloid precursor protein (APP), presenilin (PS) 1 and PS2, the APoE4 allele, and the newly identified nine genetic risk factors for late-onset AD (LOAD), altogether account for less than half of this heritability (Kamboh et al., 2012; Blumenau et al., 2020).