PSEN2 and Alzheimer disease: Although more than 90% of AD cases are late-onset (LOAD) and sporadic (sAD) with no known causal mutations [27], several disease-related mutations in the genes encoding, amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) cause early-onset AD (EOAD).