The onset and pathology of sporadic Alzheimer’s disease (sAD) seem to be affected by both sex and genetic mechanisms. Evidence supports that the high prevalence of sAD in women, worldwide, may be attributed to an interplay among aging, sex, and lifestyle, influenced by genetics, metabolic changes, and hormones. Interestingly, epigenetic mechanisms such as microRNAs (miRNAs), known as master regulators of gene expression, may contribute to this observed sexual dimorphism in sAD. To investigate the potential impact of sex-associated miRNAs on processes manifesting sAD pathology, as described by the Tau-driven Adverse Outcome Pathway (AOP) leading to memory loss. Using publicly available human miRNA datasets, sex-biased miRNAs, defined as differentially expressed by sex in tissues possibly affected by sAD pathology, were collected. In addition, sex hormone-related miRNAs were also retrieved from the literature. The compiled sex-biased and sex hormone-related miRNAs were further plugged into the dysregulated processes of the Tau-driven AOP for memory loss. Several miRNAs, previously identified as sex-associated, were implicated in dysregulated processes associated with the manifestation of sAD pathology. Importantly, the described pathology processes were not confined to a particular sex. A mechanistic-based approach utilizing miRNAs was adopted in order to elucidate the link between sex and biological processes potentially involved in the development of memory loss. The identification of sex-associated miRNAs involved in the early processes manifesting memory loss may shed light to the complex molecular mechanisms underlying sAD pathogenesis in a sex-specific manner.

中文翻译：

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性别相关的 microRNA 可能与散发性阿尔茨海默病 (sAD) 有关

散发性阿尔茨海默病（sAD）的发病和病理似乎受到性别和遗传机制的影响。有证据表明，全世界女性 SAD 的高患病率可能归因于衰老、性别和生活方式之间的相互作用，并受到遗传、代谢变化和激素的影响。有趣的是，表观遗传机制，如被称为基因表达主调节因子的 microRNA (miRNA)，可能导致了 sAD 中观察到的性别二态性。旨在研究性别相关 miRNA 对表现出 sAD 病理学过程的潜在影响，如 Tau 驱动的不良结果途径 (AOP) 所描述的导致记忆丧失。使用公开的人类 miRNA 数据集，收集了性别偏倚 miRNA（定义为可能受 sAD 病理影响的组织中按性别差异表达的 miRNA）。此外，还从文献中检索到性激素相关的miRNA。编译后的性别偏见和性激素相关 miRNA 被进一步插入 Tau 驱动的 AOP 的失调过程中，从而导致记忆丧失。一些先前被鉴定为与性别相关的 miRNA 与 sAD 病理表现相关的失调过程有关。重要的是，所描述的病理过程并不局限于特定性别。采用一种利用 miRNA 的基于机制的方法来阐明性别和可能与记忆丧失发展相关的生物过程之间的联系。鉴定参与记忆丧失早期过程的性别相关 miRNA 可能会以性别特异性方式揭示 sAD 发病机制的复杂分子机制。