Alzheimer's pathogenic mechanisms and underlying sex difference.
Alzheimer's pathogenic mechanisms and underlying sex difference.
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阿尔茨海默病的发病机制和潜在的性别差异。
DOI：
10.1007/s00018-021-03830-w
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Zhu D;Montagne A;Zhao Z
男性和女性都可能患有阿尔茨海默病(AD)，而且可能存在性别差异。AD是一种神经退行性疾病，据报道，女性的发病率高于男性：几乎三分之二的AD患者是女性。一种流行的观点是，女性的平均寿命比男性长4.5岁，而且在全球大多数亚群中，85岁或以上的女性比男性多；而老年是AD的最大风险因素。然而，相同年龄的男性和女性患阿尔茨海默病的实际风险差异很难评估，而且结果喜忧参半。越来越多的来自临床前和临床研究的证据以及估计发病率的并发症支持了性别特有的生物学机制在分散AD风险方面作为流行病学观点的重要辅助解释。虽然阿尔茨海默病患病率的一些性别差异是由于寿命的差异，但其他不同的生物机制增加了女性患阿尔茨海默病的风险和进展。这些危险因素包括1)大脑结构和生物标志物的偏差，2)心理社会应激反应，3)怀孕、更年期和性激素，4)遗传背景(即APOE)，5)炎症、胶质增生和免疫模块(即TREM2)，以及6)血管疾病。为了更好地了解阿尔茨海默病，需要对这一现象的潜在生物学机制进行更多的研究。这篇综述介绍了AD的性别差异的最新数据--AD是通往精确医学的门户，因此，塑造了专家的观点，激励研究人员朝着新的方向前进，并以更个性化的方式推动未来AD诊断工具和治疗方法的发展。
Both men and women can have Alzheimer’s disease (AD), and there might be sex differences. AD is a neurodegenerative disease, and its frequency is often reported to be higher for women than men: almost two-thirds of patients with AD are women. One prevailing view is that women live longer than men on average of 4.5 years, plus there are more women aged 85 years or older than men in most global subpopulations; and older age is the greatest risk factor for AD. However, the differences in the actual risk of developing AD for men and women of the same age is difficult to assess, and the findings have been mixed. An increasing body of evidence from preclinical and clinical studies as well as the complications in estimating incidence support the sex-specific biological mechanisms in diverging AD risk as an important adjunct explanation to the epidemiologic perspective. While some of the sex differences in AD prevalence are due to differences in longevity, other distinct biological mechanisms increase the risk and progression of AD in women. These risk factors include 1) deviations in brain structure and biomarkers, 2) psychosocial stress responses, 3) pregnancy, menopause, and sex hormones, 4) genetic background (i.e., APOE), 5) inflammation, gliosis, and immune module (i.e., TREM2), and 6) vascular disorders. More studies focusing on the underlying biological mechanisms for this phenomenon are needed to better understand AD. This review presents the most recent data in sex differences in AD – the gateway to precision medicine, therefore, shaping expert perspectives, inspiring researchers to go in new directions, and driving development of future diagnostic tools and treatments for AD in a more customized way.
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