APOE and Alzheimer disease: Individuals with Down syndrome (DS) show a much higher rate of Alzheimer disease (AD) than the general population, likely owing to the extra copy of chromosome 21.1 Yet, a large amount of variability in the clinical presentation and age at onset of AD exists among individuals with DS.2 Some of this variability may be explained by variation in the apolipoprotein E (APOE) gene on chromosome 19, with the ε4 allele of APOE associated with an increased risk for AD in both the general population and in individuals with DS.2,3,4