PSEN1 and Alzheimer disease: Interestingly, the APOE4 allele and an AD-linked PSEN1 polymorphism have each been shown to increase the risk of meiosis II chromosome segregation errors, leading to Down syndrome, and a mother carrying both the APOE4 allele and the PSEN1 polymorphism has an even higher risk of a trisomy 21 conception (Avramopoulos et al., 1996; Petersen et al., 2000; Rodriguez-Manotas et al., 2007; Bhaumik et al., 2017).