Genes related to microglia polarization and immune infiltration in Alzheimer's Disease.

IF 2.7 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Mammalian Genome Pub Date : 2024-12-01 Epub Date: 2024-10-10 DOI:10.1007/s00335-024-10073-0

Dianxia Xing, Wenjin Zhang, Yan Liu, Hong Huang, Junjie Xie

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引用次数: 0

Abstract

Alzheimer's Disease (AD) remains a significant challenge due to its complex etiology and socio-economic burden. In this study, we investigated the roles of macrophage polarization-related hub genes in AD pathology, focusing on their impact on immune infiltration and gene regulation in distinct brain regions. Using Gene Expression Omnibus (GEO) datasets GSE110226 (choroid plexus) and GSE1297 (hippocampal CA1), we identified key genes-EDN1, HHLA2, KL, TREM2, and WWTR1-associated with AD mechanisms and immune responses. Based on these findings, we developed a diagnostic model demonstrating favorable calibration and clinical applicability. Furthermore, we explored molecular interactions within mRNA-transcription factor and mRNA-miRNA regulatory networks, providing deeper insights into AD progression and identifying potential therapeutic targets. The novel identification of WWTR1 and HHLA2 as biomarkers expands the diagnostic toolkit for AD, offering new perspectives on the disease's underlying immune dynamics. However, external dataset validation and further in vitro and in vivo studies are required to confirm these results and their clinical relevance.

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与阿尔茨海默病中小胶质细胞极化和免疫浸润有关的基因。

阿尔茨海默病（AD）因其复杂的病因和社会经济负担仍是一项重大挑战。在这项研究中，我们研究了巨噬细胞极化相关枢纽基因在阿尔茨海默病病理学中的作用，重点是它们对不同脑区的免疫浸润和基因调控的影响。利用基因表达总库（GEO）数据集GSE110226（脉络丛）和GSE1297（海马CA1），我们发现了与AD机制和免疫反应相关的关键基因--EDN1、HHLA2、KL、TREM2和WWTR1。基于这些发现，我们建立了一个诊断模型，该模型具有良好的校准性和临床适用性。此外，我们还探索了mRNA-转录因子和mRNA-miRNA调控网络中的分子相互作用，从而更深入地了解了AD的发展过程，并确定了潜在的治疗靶点。WWTR1和HHLA2作为生物标记物的新发现扩展了AD的诊断工具包，为该疾病的潜在免疫动态提供了新的视角。然而，要确认这些结果及其临床意义，还需要外部数据集验证以及进一步的体外和体内研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mammalian Genome 生物-生化与分子生物学

CiteScore

4.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Mammalian Genome focuses on the experimental, theoretical and technical aspects of genetics, genomics, epigenetics and systems biology in mouse, human and other mammalian species, with an emphasis on the relationship between genotype and phenotype, elucidation of biological and disease pathways as well as experimental aspects of interventions, therapeutics, and precision medicine. The journal aims to publish high quality original papers that present novel findings in all areas of mammalian genetic research as well as review articles on areas of topical interest. The journal will also feature commentaries and editorials to inform readers of breakthrough discoveries as well as issues of research standards, policies and ethics.