APOE and Alzheimer disease: It has been well established that the APOE ɛ4 allele is associated with an increased risk of sporadic AD and younger age at onset.3,4 This association is also true in autosomal dominant forms, in which the ɛ4 allele is associated with earlier diagnoses.28 In line with this finding, we observed an association of the APOE ɛ4 allele with earlier decline in episodic memory and earlier clinical AD diagnoses in individuals with DS.