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. This evidence concerns the gene PSEN1 and early-onset autosomal dominant Alzheimer disease.