A small subpopulation (<1%) of early-onset AD patients harbor highly penetrant autosomal dominant mutations in the APP gene which encodes the amyloid precursor protein (APP), or within the PSEN1 and PSEN2 genes encoding two independent catalytic subunits of the APP protease γ-secretase, specifically presenilin-1 (PS1) and presenilin-2 (PS2) [34]. The gene discussed is PSEN2; the disease is Alzheimer disease.