APP and Alzheimer disease: A consequence of this increased life expectancy has been the emergence of age-related diseases, most importantly Alzheimer disease, which has a risk of more than 90% by the seventh decade for people with Down syndrome.6 The strong association between Alzheimer disease and Down syndrome has a genetic basis through a gene-dose effect of the amyloid precursor protein (APP) gene located on chromosome 21, which is triplicated in this population.