Neurobiology Laboratory for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Wilhelm Klein-Str. 27, CH-4012 Basel, Switzerland; Psychiatric University Clinics, University of Basel, Wilhelm Klein-Str. 27, CH-4012 Basel, Switzerland.
Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment 3 de la Faculté de Médecine, 11 rue Humann, 67000 Strasbourg, France.
Neurosci Biobehav Rev. 2016 Aug;67:89-101. doi: 10.1016/j.neubiorev.2016.04.012. Epub 2016 Apr 29.
Epidemiological studies revealed that two-thirds of Alzheimer's disease (AD) patients are women and the drop of sex steroid hormones after the menopause has been proposed to be one risk factor in AD. Similarly, the decrease of circulating testosterone levels with aging may also increase the risk of AD in men. Studies attest the neuroprotective effects of sex hormones in animal models of AD, but clinical trial data remain controversial. Here, we discuss the implication of mitochondria in gender differences observed in AD patients and animal models of AD. We summarize the role of mitochondria in aging and AD, pointing to the potential correlation between the loss of sex hormones and changes in the brain redox status. We discuss the protective effects of the sex hormones, estradiol, progesterone and testosterone with a specific focus on mitochondrial dysfunction in AD. The understanding of pathological processes linking the loss of sex hormones with mitochondrial dysfunction and mechanisms that initiate the disease onset may open new avenues for the development of gender-specific therapeutic approaches.
流行病学研究表明，三分之二的阿尔茨海默病（AD）患者为女性，绝经后性激素水平下降被认为是 AD 的一个风险因素。同样，随着年龄的增长，循环睾丸激素水平的下降也可能增加男性患 AD 的风险。研究证明，性激素对 AD 动物模型具有神经保护作用，但临床试验数据仍存在争议。在这里，我们讨论了线粒体在 AD 患者和 AD 动物模型中观察到的性别差异中的作用。我们总结了线粒体在衰老和 AD 中的作用，指出了性激素丧失与大脑氧化还原状态变化之间可能存在的相关性。我们讨论了性激素（雌二醇、孕酮和睾丸激素）的保护作用，特别关注 AD 中的线粒体功能障碍。了解将性激素丧失与线粒体功能障碍联系起来的病理过程以及引发疾病发作的机制，可能为开发针对特定性别的治疗方法开辟新途径。
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