Department of Biology and Biotechnology, La Sapienza University, Rome, Italy. rosamaria.corbo @ uniroma1.it
Dement Geriatr Cogn Disord. 2011;32(1):63-9. doi: 10.1159/000330472. Epub 2011 Aug 24.
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.
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).
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).
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.
散发性阿尔茨海默病（AD）在女性中的发病率较高，这可能是由于女性预期寿命较长，但也可能与生物性别特异性因素有关，例如女性过去的生育能力。
我们通过研究参与决定人类生育能力的卵泡刺激素受体基因（FSHR）密码子 307 和 680 处的两个多态性，研究了生育能力与女性 AD 易感性之间的关系。还研究了绝经年龄（AM）作为性别特异性 AD 易感性决定因素的作用。研究人群包括 291 名 AD 患者（70.1%为女性）和 134 名对照（63.4%为女性）。
逻辑回归分析显示，只有女性的 FSHR AS/AS 基因型与 AD 的风险显著降低相关（OR = 0.36，95%CI：0.15-0.85），表明 FSHR 基因型对 AD 易感性具有性别特异性保护作用。AD 患者的自然绝经年龄（49.7 ± 2.53）低于对照组（50.7 ± 2.53，p = 0.02），在线性回归分析中，AM 较早与 AD 发病较早之间存在关联（p = 0.004）。
遗传和非遗传性别特异性因素可能有助于女性 AD 的发病机制，但需要进一步研究以明确其实际作用。
