Importantly, while the APOE-e2 allele is relatively rare and may provide some protection against AD (Reiman et al., 2020), people who inherit one copy of the APOE-e4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk (Sando et al., 2008; Reiman et al., 2020). This evidence concerns the gene APOE and Alzheimer disease.