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免疫细胞和炎症因子对阿尔茨海默病轴的影响:来自中介孟德尔随机化研究的证据

Influence of immune cells and inflammatory factors on Alzheimer's disease axis: evidence from mediation Mendelian randomization study.

作者信息

Zhang Jianxin, Fan Wenhui, Su Chen, Jin Zhi

机构信息

Department of Traditional Chinese Medicine, the Second Hospital of Shandong University, Jinan, 250014, China.

出版信息

BMC Neurol. 2025 Feb 5;25(1):49. doi: 10.1186/s12883-025-04057-z.

DOI:10.1186/s12883-025-04057-z
PMID:39910474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11796147/
Abstract

BACKGROUND

Alzheimer's disease (AD) is one of the most common forms of dementia in the elderly, characterized by progressive neurodegeneration. While the exact etiology of AD remains unclear, immune inflammation is known to play a significant role in the disease.

METHODS

This study utilized a two-sample Mendelian randomization (MR) approach to assess the causal relationship between different types of immune cells and AD, while considering inflammatory factors as intermediate variables. Data were collected from three sources: immune cell data (731 phenotypes), inflammatory factors (48 cytokines from 8,293 individuals), and AD data (35,274 cases, 59,163 controls). Multiple MR methods were employed to minimize bias, and detailed descriptions of instrumental variable selection and statistical methods were provided.

RESULTS

The study findings suggest potential causal relationships between six different types of immune cells and AD, as well as causal relationships between 13 immune cells and inflammatory factors. Additionally, two statistically significant inflammatory factors were found to have potential causal relationships with AD. Specifically, immune cells CD33-HLA DR + and CD45 on CD33-HLA DR + may further influence AD by regulating Interleukin-2 levels.

CONCLUSION

This study provides valuable insights into the immunoinflammatory pathogenesis of AD and offers partial guidance for the development of relevant interventions, thereby contributing beneficial information for the prevention and treatment of related diseases.

摘要

背景

阿尔茨海默病(AD)是老年人中最常见的痴呆形式之一,其特征为进行性神经退行性变。虽然AD的确切病因尚不清楚,但已知免疫炎症在该病中起重要作用。

方法

本研究采用两样本孟德尔随机化(MR)方法来评估不同类型免疫细胞与AD之间的因果关系,同时将炎症因子视为中间变量。数据收集自三个来源:免疫细胞数据(731种表型)、炎症因子(来自8293人的48种细胞因子)和AD数据(35274例病例,59163例对照)。采用多种MR方法以尽量减少偏差,并提供了工具变量选择和统计方法的详细描述。

结果

研究结果表明六种不同类型的免疫细胞与AD之间存在潜在因果关系,以及13种免疫细胞与炎症因子之间存在因果关系。此外,发现两种具有统计学意义的炎症因子与AD存在潜在因果关系。具体而言,免疫细胞CD33-HLA DR+和CD33-HLA DR+上的CD45可能通过调节白细胞介素-2水平进一步影响AD。

结论

本研究为AD的免疫炎症发病机制提供了有价值的见解,并为相关干预措施的开发提供了部分指导,从而为相关疾病的预防和治疗提供有益信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/fd3eacedd4b2/12883_2025_4057_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/6ca681d0b91b/12883_2025_4057_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/4dfba31403f1/12883_2025_4057_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/87737a2ea4bc/12883_2025_4057_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/fd3eacedd4b2/12883_2025_4057_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/6ca681d0b91b/12883_2025_4057_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/4dfba31403f1/12883_2025_4057_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/87737a2ea4bc/12883_2025_4057_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728c/11796147/fd3eacedd4b2/12883_2025_4057_Fig2_HTML.jpg

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本文引用的文献

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J Control Release. 2024 Nov;375:346-365. doi: 10.1016/j.jconrel.2024.09.012. Epub 2024 Sep 18.
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Emerging Roles of Adaptive Immune Response in Alzheimer's Disease.适应性免疫反应在阿尔茨海默病中的新作用
Aging Dis. 2024 Aug 14. doi: 10.14336/AD.2024.0564.
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Roles of Cytokines in Alzheimer's Disease.细胞因子在阿尔茨海默病中的作用。
Int J Mol Sci. 2024 May 26;25(11):5803. doi: 10.3390/ijms25115803.
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Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model.外周免疫细胞的年轻化可减轻小鼠模型的阿尔茨海默病样病理和行为缺陷。
Sci Adv. 2024 May 31;10(22):eadl1123. doi: 10.1126/sciadv.adl1123. Epub 2024 May 29.
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Neuroinflammation is associated with Alzheimer's disease co-pathology in dementia with Lewy bodies.神经炎症与路易体痴呆中的阿尔茨海默病共病病理相关。
Acta Neuropathol Commun. 2024 May 7;12(1):73. doi: 10.1186/s40478-024-01786-z.
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Iron metabolism disorder and multiple sclerosis: a comprehensive analysis.铁代谢紊乱与多发性硬化症:全面分析。
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HuM195 and its single-chain variable fragment increase Aβ phagocytosis in microglia via elimination of CD33 inhibitory signaling.HuM195 及其单链可变片段通过消除 CD33 抑制性信号来增加小神经胶质细胞对 Aβ 的吞噬作用。
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Causal relationship between immune cells and neurodegenerative diseases: a two-sample Mendelian randomisation study.免疫细胞与神经退行性疾病之间的因果关系:两样本孟德尔随机研究。
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