Collectively, the genetic etiology of AD is very complex: early-onset AD (less than 5% of cases) is often familial (fAD) with autosomal dominant and fully penetrant inheritance and can be caused by any of more than 200 pathogenic mutations in APP (33 mutations, duplication), PSEN1 (185 mutations) and PSEN2 (13 mutations; http://www.molgen.ua.ac.be/ADmutations). Here, APP is linked to Alzheimer disease.