Huang Shiwei, Zhong Lily, Zheng Lilly, Shi Jian
Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Neurology, Department of Veterans Affairs Health Care System, San Francisco and University of California, San Francisco, CA 94121, USA.
Genes (Basel). 2025 Aug 11;16(8):943. doi: 10.3390/genes16080943.
Alzheimer's disease (AD) affects approximately 50 million people worldwide, with women comprising two-thirds of those affected. Despite this disproportionate impact, the sex-specific pathological mechanisms underlying AD in women remain poorly understood, and female-specific biomarkers have been significantly understudied. This critical knowledge gap requires focused research to improve diagnostic and therapeutic approaches for women with AD. In this review, we systematically examine the pathological mechanisms underlying AD in women, including sex-related differences in inflammation, autophagy, and metabolic dysfunction. We further explore microRNA (miRNA) expression patterns and evaluate miRNA candidates as potential biomarkers for AD in women based on current literature. Through this analysis, we identified approximately 20 miRNA candidates derived from diverse human samples, including brain tissue, blood, and cerebrospinal fluid, in multiple independent studies. These candidates demonstrate the potential for developing accessible, non-invasive biomarkers, particularly those identified in blood and cerebrospinal fluid. However, the limited overlap between studies highlights that female-specific miRNA biomarker research for AD remains in its early discovery phase, emphasizing the urgent need for large-scale validation studies and standardized methodological approaches to advance this promising field for clinical application.
阿尔茨海默病（AD）在全球约影响5000万人，其中三分之二为女性患者。尽管有这种不成比例的影响，但AD在女性中的性别特异性病理机制仍知之甚少，针对女性的特异性生物标志物的研究也明显不足。这一关键的知识空白需要开展针对性研究，以改善AD女性患者的诊断和治疗方法。在本综述中，我们系统地研究了AD在女性中的病理机制，包括炎症、自噬和代谢功能障碍方面的性别差异。我们进一步探讨了微小RNA（miRNA）的表达模式，并根据现有文献评估miRNA候选物作为AD女性患者潜在生物标志物的可能性。通过这一分析，我们在多项独立研究中从包括脑组织、血液和脑脊液在内的多种人类样本中确定了约20种miRNA候选物。这些候选物显示出开发便捷、非侵入性生物标志物的潜力，尤其是那些在血液和脑脊液中发现的生物标志物。然而，研究之间有限的重叠表明，AD女性特异性miRNA生物标志物研究仍处于早期发现阶段，这突出表明迫切需要进行大规模验证研究和标准化方法，以推动这一有前景的领域用于临床应用。
