Age-related inflammatory diseases -: Role of genetics and gender in the pathophysiology of Alzheimer's disease
Age-related inflammatory diseases -: Role of genetics and gender in the pathophysiology of Alzheimer's disease
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DOI：
10.1196/annals.1386.008
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发表时间：
2006-01-01
期刊：
影响因子：
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通讯作者：
Caruso, Calogero
中科院分区：
文献类型：
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作者：
Candore, Giuseppina;Balistreri, Carmela R.;Caruso, Calogero
阿尔茨海默病（AD）是一种异质性、进行性神经退行性疾病，在西方社会主要导致临床痴呆。很大一部分女性患有这种疾病，尤其是在高龄女性，这可能在很大程度上与女性寿命更长有关。然而，一些研究表明，女性的发病率可能确实更高。因此，雌激素对大脑的影响以及更年期期间雌激素的减少引起了人们的特别关注。绝经后，雌激素的循环水平显着下降，影响了预计会影响 AD 风险的几个大脑过程。雌激素对氧化应激、炎症和脑血管系统的控制也可能会增加 AD 风险。在妇女健康倡议记忆研究（一项针对 6579 岁女性的随机、安慰剂对照试验）中，口服雌激素加孕激素被发现会使患痴呆症的几率增加一倍，并且在治疗开始后不久就会出现风险。因此，根据目前的证据，激素疗法 (HT) 不适用于预防 AD。炎症明显发生在 AD 大脑的病理脆弱区域，对影响 AD 发病机制的遗传因素的研究已导致鉴定出许多充当易感性调节剂的基因多态性。因此，一些报告表明AD的风险很大程度上受到编码炎症介质的基因的启动子区域或其他非翻译区域中的几种遗传多态性的影响。在这里，我们回顾了一些数据，这些数据表明炎症遗传变异也可能导致女性患 AD 的易感性更高。总之，这些信息可能代表了未来识别高危个体以及实现药物反应的药物基因组学方法的基础。
Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western societies mainly accounts for clinical dementia. A high proportion of women are affected by this disease, especially at a very advanced age, which might to a large extent be associated with the fact that women live longer. However, some studies suggest that incidence rates may be really increased in women. For this reason the influence of estrogens on the brain and the decrease of it during menopause are of special interest. After menopause, circulating levels of estrogens markedly decline, influencing several brain processes predicted to influence AD risk. The control of estrogens on oxidative stress, inflammation, and the cerebral vasculature might also be expected to increase AD risk. During the Women's Health Initiative Memory Study-a randomized, placebo-controlled trial of women 6579 years of age-oral estrogen plus progestin was seen to double the rate of developing dementia, with risk appearing soon after the treatment was initiated. On the basis of current evidence, hormone therapy (HT) is thus not indicated for the prevention of AD. Inflammation clearly occurs in pathologically vulnerable regions of the AD brain and the search for genetic factors influencing the pathogenesis of AD has led to the identification of numerous gene polymorphisms that act as susceptibility modifiers. Accordingly, several reports have indicated that the risk of AD is substantially influenced by several genetic polymorphisms in the promoter region, or other untranslated regions, of genes encoding inflammatory mediators. Here we review several data suggesting that inflammatory genetic variation may contribute to higher AD susceptibility in women too. All together this information may represent the basis both for future recognition of individuals at risk as well as for a pharmacogenomic approach in achieving drug responsiveness.