Influence of Variation in the Follicle-Stimulating Hormone Receptor Gene (FSHR) and Age at Menopause on the Development of Alzheimer’s Disease in Women

Abstract

Background: The higher prevalence of sporadic Alzheimer’s disease (AD) in women may be explained by their longer life expectancy, but also by biological gender-specific factors such as a woman’s past fertility. Methods: We investigated the relationship between fertility and susceptibility to AD in women by studying two polymorphisms at codons 307 and 680 of the follicle-stimulating hormone receptor gene (FSHR) involved in determining human fertility. The role of age at menopause (AM) as a gender-specific AD susceptibility determinant was also examined. The study population comprised 291 AD patients (70.1% women) and 134 controls (63.4% women). Results: Logistic regression analysis showed that only among the women the FSHR AS/AS genotype was associated with a significantly lower risk of AD (OR = 0.36, 95% CI: 0.15–0.85), suggesting a gender-specific protective role of the FSHR genotype against AD susceptibility. A lower age at natural menopause was observed in the AD patients (49.7 ± 2.53) than in the controls (50.7 ± 2.53, p = 0.02) and on linear regression analysis an association emerged between an earlier AM and an earlier AD onset (p = 0.004). Conclusions: Genetic and non-genetic gender-specific factors may contribute to the AD pathogenesis in women, although further investigations are required to clarify their actual role.