Sex differences exist in the onset and progression of Alzheimer’s disease. Globally, women have a higher prevalence, while men with Alzheimer’s disease experience earlier mortality and more pronounced cognitive decline than women. The cause of sex differences in Alzheimer’s disease remains unclear. Accumulating evidence suggests the potential role of X-linked genetic factors in the sex difference of Alzheimer’s disease (AD). During embryogenesis, a remarkable process known as X-chromosome inactivation (XCI) occurs in females, leading to one of the X chromosomes undergoing transcriptional inactivation, which balances the effects of two X chromosomes in females. Nevertheless, certain genes exceptionally escape from XCI, which provides a basis for dual expression dosage of specific genes in females. Based on recent research findings, we explore key escape genes and their potential therapeutic use associated with Alzheimer’s disease. Also, we discuss their possible role in driving the sex differences in Alzheimer’s disease. This will provide new perspectives for precision medicine and gender-specific treatment of AD.

中文翻译：

---

逃离阿尔茨海默病的 X 染色体失活和性别差异

阿尔茨海默病的发病和进展存在性别差异。在全球范围内，女性的患病率较高，而患有阿尔茨海默病的男性比女性死亡率更早，认知能力下降更明显。阿尔茨海默病性别差异的原因尚不清楚。越来越多的证据表明 X 连锁遗传因素在阿尔茨海默病 (AD) 的性别差异中具有潜在作用。在胚胎发生过程中，女性体内会发生一种被称为 X 染色体失活 (XCI) 的显着过程，导致其中一条 X 染色体发生转录失活，从而平衡女性体内两条 X 染色体的作用。然而，某些基因异常地从XCI中逃脱，这为雌性中特定基因的双重表达剂量提供了基础。根据最近的研究结果，我们探索了关键的逃逸基因及其与阿尔茨海默病相关的潜在治疗用途。此外，我们还讨论了它们在推动阿尔茨海默病性别差异中可能发挥的作用。这将为精准医学和 AD 的性别特异性治疗提供新的视角。