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Microglia are believed to modulate AD by limiting the expansion of amyloid plaques that contribute to disease pathology. To understand the effect of APOE genotype on microglia function, the authors isolated microglia from APOE ε3/ε3 or APOE ε3/ε4 patients with AD as well as age-matched healthy control individuals and performed single-nucleus RNA sequencing, observing that microglia from women who carried the APOE ε4 allele were highly enriched for genes linked to degranulation signaling in neutrophils, a key peripheral immune cell type.

据信小胶质细胞通过限制导致疾病病理的淀粉样斑块的扩张来调节AD。为了了解载脂蛋白E基因型对小胶质细胞功能的影响，作者从载脂蛋白Eε3/ε3或载脂蛋白Eε3/ε4 AD患者以及年龄匹配的健康对照个体中分离出小胶质细胞，并进行了单核RNA测序，观察到携带载脂蛋白Eε4等位基因的女性的小胶质细胞高度富集了与中性粒细胞脱粒信号相关的基因，中性粒细胞是一种关键的外周免疫细胞类型。

Neutrophil degranulation signaling was also associated with the severity of tauopathy in women who carried the APOE ε4 allele, which suggests that neutrophils might contribute to AD risk in these patients.The authors next performed RNA sequencing on neutrophils from men and women with mild cognitive impairment or AD, using samples from cognitively unimpaired individuals as a benchmark.

中性粒细胞脱颗粒信号传导也与携带APOEε4等位基因的女性tau蛋白病的严重程度有关，这表明中性粒细胞可能会增加这些患者的AD风险。接下来，作者使用来自认知未受损个体的样本作为基准，对患有轻度认知障碍或AD的男性和女性的中性粒细胞进行RNA测序。

Neutrophils from healthy women who carried the APOE ε4 allele displayed signs of accelerated immune aging when compared to neutrophils from APOE ε3/ε3 individuals. Additionally, neutrophils from cognitively impaired women who carried the APOE ε4 allele exhibited greater expression of genes linked to interleukin (IL)-17 cytokine signaling, or immunosuppressive pathways involving IL-10, IL-18 and TGFβ.

与来自APOEε3/ε3个体的嗜中性粒细胞相比，携带APOEε4等位基因的健康女性的嗜中性粒细胞显示出加速免疫衰老的迹象。此外，携带APOEε4等位基因的认知障碍女性的中性粒细胞表现出与白细胞介素（IL）-17细胞因子信号传导或涉及IL-10，IL-18和TGFβ的免疫抑制途径相关的基因的更高表达。

IL-17+ neutrophils were also more capable of infiltrating the brains of APOE ε3/ε4 women with AD and were observed to interact with microglia..

IL-17+中性粒细胞也更能浸润患有AD的APOEε3/ε4女性的大脑，并被观察到与小胶质细胞相互作用。。

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Author informationAuthors and AffiliationsNature Aging https://www.nature.com/nataging/George Andrew S. InglisAuthorsGeorge Andrew S. InglisView author publicationsYou can also search for this author in

作者信息作者和附属机构年龄https://www.nature.com/nataging/GeorgeAndrew S.InglisAuthorsGeorge Andrew S.InglisView作者出版物您也可以在

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George Andrew S. Inglis.Rights and permissionsReprints and permissionsAbout this articleCite this articleInglis, G.A.S. Exploring how APOE ε4 increases Alzheimer’s disease risk in women.

乔治·安德鲁·英格利斯。权利和许可打印和许可本文引用这篇文章，G.A.S.探索APOEε4如何增加女性患阿尔茨海默氏病的风险。

Nat Aging (2024). https://doi.org/10.1038/s43587-024-00698-wDownload citationPublished: 12 August 2024DOI: https://doi.org/10.1038/s43587-024-00698-wShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Nat Aging（2024）。https://doi.org/10.1038/s43587-024-00698-wDownload引文发布日期：2024年8月12日OI：https://doi.org/10.1038/s43587-024-00698-wShare本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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