PSEN1 and Alzheimer disease: Five PSEN1 mutations (e.g., p.Met146Leu, p.His163Arg, p.Ala246Glu, p.Leu286val, p.Cys410Tyr) were originally discovered in 1995 on human chromosome 14 (14q24.3) by genetic analysis of six large pedigrees with Alzheimer disease (AD)4.