Variation at follicle stimulating hormone receptor (FSHR) gene and age at natural menopause influence the onset of Alzheimer’s disease in women.

There is evidence of a higher prevalence of Alzheimer’s disease (AD) in women, and it is becoming clear that it may be due not only to their longer life expectancy, but also to biological risk factors. In previous investigations we observed that, in addition to genes involved in estrogen metabolism (ESR1 and CYP19), also gender-specific factors such as past fertility may play a relevant role in the development of AD in women. In the present study we investigated the possible influence on AD onset of FSHR gene, that is involved in the regulation of fertility in women. As a possible AD risk factor, age at natural menopause was examined as well. In a sample of 212 women with late-onset sporadic AD and 85 controls the FSHR Thr307Ala (rs 6165) polymorphism was examined. A significant excess of FSHR GG genotype (Ala/Ala) (OR = 0.46 , 95% CI 0.24-0.90, p=0.02) was observed in controls suggesting that Ala/Ala genotype could have a protective effect on AD development in women. AD women had an age at natural menopause (49.7± 0.21) lower than controls (50.6± 0.34, p=0.02) and linear regression analysis showed a significant positive relationship (p=0.03) between age at natural menopause and age at AD onset. These observations seem to support the hypothesis that the loss of neuroprotective estrogens after menopause may play a role in AD development in women.