Identification of key lipid metabolism-related genes in Alzheimer’s disease

Lipids in Health and Disease

Research

Youjie Zeng¹  Guoxin Lin¹  Si Cao¹  Juan Tang²  Nannan Li² 

[1] Department of Anesthesiology, Third Xiangya Hospital, Central South University, 410013, Changsha, Hunan, China;Department of Nephrology, Third Xiangya Hospital, Central South University, 410013, Changsha, Hunan, China;

关键词: Alzheimer's disease;    Bioinformatics;    Biomarkers;    Lipid metabolism;    Differentially expressed genes;    Differential expression analysis;    Hub genes;    Immune cell infiltration;    Key genes;   

DOI  :  10.1186/s12944-023-01918-9

 received in 2023-06-22, accepted in 2023-09-04,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAlzheimer’s disease (AD) represents profound degenerative conditions of the brain that cause significant deterioration in memory and cognitive function. Despite extensive research on the significant contribution of lipid metabolism to AD progression, the precise mechanisms remain incompletely understood. Hence, this study aimed to identify key differentially expressed lipid metabolism-related genes (DELMRGs) in AD progression.MethodsComprehensive analyses were performed to determine key DELMRGs in AD compared to controls in GSE122063 dataset from Gene Expression Omnibus. Additionally, the ssGSEA algorithm was utilized for estimating immune cell levels. Subsequently, correlations between key DELMRGs and each immune cell were calculated specifically in AD samples. The key DELMRGs expression levels were validated via two external datasets. Furthermore, gene set enrichment analysis (GSEA) was utilized for deriving associated pathways of key DELMRGs. Additionally, miRNA-TF regulatory networks of the key DELMRGs were constructed using the miRDB, NetworkAnalyst 3.0, and Cytoscape software. Finally, based on key DELMRGs, AD samples were further segmented into two subclusters via consensus clustering, and immune cell patterns and pathway differences between the two subclusters were examined.ResultsSeventy up-regulated and 100 down-regulated DELMRGs were identified. Subsequently, three key DELMRGs (DLD, PLPP2, and PLAAT4) were determined utilizing three algorithms [(i) LASSO, (ii) SVM-RFE, and (iii) random forest]. Specifically, PLPP2 and PLAAT4 were up-regulated, while DLD exhibited downregulation in AD cerebral cortex tissue. This was validated in two separate external datasets (GSE132903 and GSE33000). The AD group exhibited significantly altered immune cell composition compared to controls. In addition, GSEA identified various pathways commonly associated with three key DELMRGs. Moreover, the regulatory network of miRNA-TF for key DELMRGs was established. Finally, significant differences in immune cell levels and several pathways were identified between the two subclusters.ConclusionThis study identified DLD, PLPP2, and PLAAT4 as key DELMRGs in AD progression, providing novel insights for AD prevention/treatment.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

13690_2023_1170_Article_IEq78.gif

13690_2023_1170_Article_IEq76.gif

12888_2023_5142_Article_IEq12.gif

Fig. 4

Fig. 3

Fig. 3

40798_2023_628_Figg_HTML.png

Fig. 1

40249_2023_1135_Article_IEq6.gif

Fig. 2