PSEN2 and Alzheimer disease: Accumulation of Aβ in the brain is associated with disease-causing inherited variants of the amyloid precursor protein (APP) [3], presenilin 1 (PS1) [4], presenilin 2 (PS2) [5], and apoplipoprotein E (APOE) [6] genes, and an increased extracellular Aβ level is a major cause of neuronal death in AD.