Mapping of the chromosome 21 APP gene, from which is cleaved the Aβ fragment present in plaques in DS and AD [61,71], together with the discovery of mutations in chromosome 21 genes that are linked to familial AD [71] and the virtual certain prediction of precocious development of AD present in those with trisomy 21 [14], lent credence to the importance of chromosome 21 genes in the development of AD [68]. Here, APP is linked to Alzheimer disease.