Growing evidence supports significant involvement of immune dysfunction in the etiology of neurodegenerative diseases, several of which also display prominent sex differences across prevalence, pathology, and symptomology. In this review, we summarize evidence from human studies of established and recent findings of sex differences in multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis and discuss how sex-specific central nervous system innate immune activity could contribute to downstream sex differences in these diseases. We examine human genomic and transcriptomics studies in each neurodegenerative disease through the lens of sex differences in the neuroimmune system and highlight the importance of stratifying sex in clinical and translational research studies. Finally, we discuss the limitations of the existing studies and outline recommendations for further advancing sex-based analyses to uncover novel disease mechanisms that could ultimately help treat both sexes.

越来越多的证据支持免疫功能障碍在神经退行性疾病的病因学中发挥重要作用，其中一些神经退行性疾病在患病率、病理学和症状学方面也表现出显着的性别差异。在这篇综述中，我们总结了人类研究中关于多发性硬化症、阿尔茨海默病、帕金森病和肌萎缩侧索硬化症性别差异的既定和最新发现的证据，并讨论了性别特异性中枢神经系统先天免疫活动如何导致下游性别差异在这些疾病中。我们通过神经免疫系统中性别差异的视角来检查每种神经退行性疾病的人类基因组和转录组学研究，并强调临床和转化研究中性别分层的重要性。最后，我们讨论了现有研究的局限性，并概述了进一步推进基于性别的分析的建议，以揭示最终有助于治疗两性的新疾病机制。