One notable example is the apolipoprotein E (APOE) polymorphic alleles, as APOE-ɛ2 allele carriers have reduced Alzheimer’s disease risk.17–19 In addition, recent studies have suggested that the genetic architecture of resilience is distinct from that of clinical Alzheimer’s disease with only a small contribution of APOE,20 suggesting that uncovering the genetic architecture of resilience may provide new insight into genomic pathways of protection. Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.