Influence of variation in the follicle-stimulating hormone receptor gene (FSHR) and age at menopause on the development of Alzheimer's disease in women.

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.