Background. An increased risk of Alzheimer's disease (AD) has been reported in young mothers of Down's syndrome (DS) probands. Allele ε4 of the apolipoprotein E (apoE) gene is a genetic susceptibility factor for AD. We examined the distribution of apoE alleles in people with DS and their parents. Methods. We studied 188 Danish people with non-mosaic, free trisomy 21 of known parental origin (determined by DNA polymorphism analysis), and their parents, chosen from a population-based study of DS, and compared the frequency of apoE alleles with a previously published Danish control sample. Findings. In people with DS, there was no significant difference in apoE allele distribution compared with controls. The frequency of allele ε4 in the fathers (11.8%) was significantly lower than in controls (17.4%, p = 0.02). The frequency of allele ε4 in the mothers (19.4%) was not significantly different from that of controls. Nevertheless, in young mothers with a meiosis II error, ε4 frequency was 30.0%, significantly higher than in older mothers with a meiosis II error (13.0%, p = 0.03). Interpretation. We suggest that apoE allele ε4 is a risk factor for meiosis II non-disjunction in young mothers, but the biological role of apoE in oocytes remains to be investigated.
ASJC Scopus subject areas