PSEN1 and Alzheimer disease: al. study also suggests a potential gene-gene interaction between PSEN1 and APOE. Specifically, it suggests that E318G carriers who are also heterozygous carriers of the APOEε4 allele have a similar AD risk as individuals who are homozygous for APOEε4 and twice the risk of those heterozygous for APOEε4 without the E318G allele.