Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
Neuroscience Graduate Program, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA.
Cell Mol Life Sci. 2021 Jun;78(11):4907-4920. doi: 10.1007/s00018-021-03830-w. Epub 2021 Apr 12.
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. Although 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.
AD 是一种神经退行性疾病，其发病率常被报道为女性高于男性：近三分之二的 AD 患者为女性。一种流行的观点认为，女性的平均寿命比男性长 4.5 年，而且在大多数全球亚人群中，85 岁或以上的女性人数多于男性；而年龄越大，患 AD 的风险就越大。然而，对于相同年龄的男性和女性患 AD 的实际风险差异很难评估，而且研究结果也不一致。越来越多的临床前和临床研究证据以及发病率估算中的并发症支持 AD 风险存在性别特异性生物学机制，这是对流行病学观点的重要补充解释。尽管 AD 患病率的一些性别差异归因于寿命的差异，但其他不同的生物学机制会增加女性患 AD 的风险和进展。这些风险因素包括：（1）大脑结构和生物标志物的差异；（2）心理社会应激反应；（3）妊娠、绝经和性激素；（4）遗传背景（即 APOE）；（5）炎症、神经胶质增生和免疫模块（即 TREM2）；以及（6）血管疾病。需要更多关注这一现象背后的生物学机制的研究，以更好地了解 AD。本文综述了 AD 中性别差异的最新数据——精准医学的切入点，因此，这塑造了专家观点，激励研究人员朝着新的方向发展，并推动 AD 未来诊断工具和治疗方法的发展，使其更具个性化。
