记忆性CD8+ T细胞的衰老基因标记与阿尔茨海默病的神经认知功能相关

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY Immunity & Ageing Pub Date : 2023-12-02 DOI:10.1186/s12979-023-00396-y
Juan Joseph Young, Hong-Jai Park, Minhyung Kim, Jennefer Par-Young, Hugh Bartlett, Hye Sun Kim, Serhan Unlu, Lais Osmani, Min Sun Shin, Richard Bucala, Christopher H van Dyck, Heather Allore, Adam P Mecca, Sungyong You, Insoo Kang
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引用次数: 0

摘要

背景:记忆性CD8+ T细胞随年龄增长而扩增。我们之前证明了在没有阿尔茨海默病(AD)的老年人外周血中表达低水平IL-7受体α (il - 7r α低)的效应记忆(EM) CD8+ T细胞的年龄相关扩张及其基因标记(即il - 7r α低衰老基因)的存在。考虑到年龄是AD的最强危险因素,以及最近在AD中发现EM CD8+ T细胞扩增,主要是il - 7r α低细胞,我们研究了AD患者是否有il - 7r α低衰老基因特征的改变,特别是与AD和疾病严重程度可能相关的基因。结果:通过对公开数据集的系统搜索,我们确定了一组29个候选基因(即假定的AD基因),这些基因可能在AD患者的外周血中差异表达。29个AD基因中,il - 7r α低衰老基因9个(31%)为AD低衰老基因(P)。通过对认知正常人(CN, 38例)和AD患者(轻度认知障碍40例,痴呆43例)外周血中40个基因的RT-qPCR分析,包括29个AD推定基因,另外9个IL-7R低衰老但不包括AD推定基因,2个炎症控制基因,验证了上述发现。RT-qPCR结果显示AD组与CN组有8个差异表达基因;其中5个(62.5%)是il - 7r α低衰老基因(FGFBP2、GZMH、NUAK1、PRSS23、TGFBR3),此前未报道在AD中发生改变。无偏聚类分析显示,MoCA、CDRsob和神经心理测试结果显示,所分析的40个基因(包括il - 7r α低衰老基因)在痴呆患者中有3组表达水平不同。结论:我们报道了AD患者外周血中与il - 7r α低EM CD8+ T细胞相关的“正常”衰老基因的差异表达,以及该基因表达在AD痴呆患者聚类为不同认知功能水平组中的意义。这些结果为研究与年龄相关的免疫变化(包括与CD8+ T细胞相关的免疫变化)在AD中的可能影响提供了一个平台。
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Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer's disease.

Background: Memory CD8+ T cells expand with age. We previously demonstrated an age-associated expansion of effector memory (EM) CD8+ T cells expressing low levels of IL-7 receptor alpha (IL-7Rαlow) and the presence of its gene signature (i.e., IL-7Rαlow aging genes) in peripheral blood of older adults without Alzheimer's disease (AD). Considering age as the strongest risk factor for AD and the recent finding of EM CD8+ T cell expansion, mostly IL-7Rαlow cells, in AD, we investigated whether subjects with AD have alterations in IL-7Rαlow aging gene signature, especially in relation to genes possibly associated with AD and disease severity.

Results: We identified a set of 29 candidate genes (i.e., putative AD genes) which could be differentially expressed in peripheral blood of patients with AD through the systematic search of publicly available datasets. Of the 29 putative AD genes, 9 genes (31%) were IL-7Rαlow aging genes (P < 0.001), suggesting the possible implication of IL-7Rαlow aging genes in AD. These findings were validated by RT-qPCR analysis of 40 genes, including 29 putative AD genes, additional 9 top IL-7R⍺low aging but not the putative AD genes, and 2 inflammatory control genes in peripheral blood of cognitively normal persons (CN, 38 subjects) and patients with AD (40 mild cognitive impairment and 43 dementia subjects). The RT-qPCR results showed 8 differentially expressed genes between AD and CN groups; five (62.5%) of which were top IL-7Rαlow aging genes (FGFBP2, GZMH, NUAK1, PRSS23, TGFBR3) not previously reported to be altered in AD. Unbiased clustering analysis revealed 3 clusters of dementia patients with distinct expression levels of the 40 analyzed genes, including IL-7Rαlow aging genes, which were associated with neurocognitive function as determined by MoCA, CDRsob and neuropsychological testing.

Conclusions: We report differential expression of "normal" aging genes associated with IL-7Rαlow EM CD8+ T cells in peripheral blood of patients with AD, and the significance of such gene expression in clustering subjects with dementia due to AD into groups with different levels of cognitive functioning. These results provide a platform for studies investigating the possible implications of age-related immune changes, including those associated with CD8+ T cells, in AD.

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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
期刊最新文献
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