Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.
Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, California, USA.
Alzheimers Dement. 2024 Jul;20(7):5062-5070. doi: 10.1002/alz.13892. Epub 2024 Jun 3.
Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early-onset Alzheimer's disease (EOAD).
We examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital polymerase chain reaction (ddPCR) data from CD4 T cells from participants with EOAD and clinically normal controls.
We analyzed PBMCs from 16 individuals by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAG T cells in EOAD. Isolating CD4 T cells from 19 individuals, including four cases analyzed by scRNA-seq, we confirmed increased expression of ISAG marker genes. Publicly available cerebrospinal fluid leukocyte scRNA-seq data from late-onset mild cognitive impairment and AD also revealed increased expression of interferon-response genes.
Antiviral-like ISAG T cells are expanded in EOAD. Additional research into these cells and the role of heightened peripheral IFN signaling in neurodegeneration is warranted.
Interferon-responsive T cells expanded in early-onset Alzheimer's disease (AD). Increased interferon-associated gene expression present in early- and late-onset AD. Peripheral immune changes in T and NK cells driven by females with early-onset AD.
改变的免疫特征正在成为神经退行性疾病的一个核心主题，然而，对于早发性阿尔茨海默病（EOAD）中的免疫反应知之甚少。
我们检查了来自 EOAD 患者和临床正常对照者外周血单核细胞（PBMC）的单细胞 RNA 测序（scRNA-seq）数据和 CD4 T 细胞的数字聚合酶链反应（ddPCR）数据。
我们通过 scRNA-seq 分析了 16 个人的 PBMC，发现 EOAD 中干扰素信号相关基因（ISAG）表达增加，抗病毒样 ISAG T 细胞显著扩增。从 19 个人中分离 CD4 T 细胞，包括通过 scRNA-seq 分析的四个病例，我们证实了 ISAG 标记基因的表达增加。来自晚发性轻度认知障碍和 AD 的公共脑脊液白细胞 scRNA-seq 数据也显示干扰素反应基因表达增加。
抗病毒样 ISAG T 细胞在 EOAD 中扩增。需要进一步研究这些细胞以及外周 IFN 信号增强在神经退行性变中的作用。
干扰素反应性 T 细胞在早发性阿尔茨海默病（AD）中扩增。早发和晚发 AD 中存在干扰素相关基因表达增加。由早发性 AD 女性驱动的 T 和 NK 细胞中的外周免疫变化。
