Contrasting with the relatively minor (5–10%) cases of autosomal dominant AD, the major sporadic AD cases are not associated with gene mutations of either the amyloid precursor protein (APP) or one of the two components of the γ-secretase complex, presenilins 1 and 2, in shifting the APP processing toward formation of amyloid-β42. The gene discussed is APP; the disease is Alzheimer disease.