Combined effect of apolipoprotein e genotype and past fertility on age at onset of Alzheimer's disease in women.

Background: Various risk factors influence the development of Alzheimer's disease (AD). Apolipoprotein E (APOE) e * 4 allele has a major role in AD susceptibility and its presence reduces age at AD onset. APOE is also thought to influence human reproduction, and common APOE genotypes seem to be associated with differential fertility. With this study, we investigated possible relationships between APOE genotype, past fertility, and AD onset age. Methods: APOE genotypes were determined in a sample of 176 women with sporadic AD. The number of children each woman had delivered was recorded. Results: A comparison of APOE genotype distribution in parous and nulliparous AD women confirmed that the e * 3/e * 3 genotype is associated with higher fertility and the e * 4-carrying genotypes with lower fertility. When the combined effects of fertility and APOE genotypes on AD onset age were analyzed, parity was found to be associated with a significantly lower AD onset age (73.8 8 6.2 years) than nulliparity (80.7 8 5.0 years; p = 0.0007) among subjects carrying e * 3/e * 3 and e * 3/e * 2 genotypes. A similar effect was absent among e * 4 carriers. Considering the high frequency of e * 3/e * 3 plus e * 3/e * 2 genotypes in Europe (range: 63-87%), past fertility may influence AD onset age in many women. Conclusion: Past fertility may have a relevant effect on AD onset age and this effect is influenced by APOE genotype.