Mining of core genes and analysis of related pathways in Alzheimer's disease based on bioinformatic analysis

ZHANG Hong; ZHAN Shuqin

doi:10.7619/jcmp.20242038

Journal of Clinical Medicine in Practice > 2024 > 28(19): 22-26, 32. > DOI: 10.7619/jcmp.20242038

ZHANG Hong, ZHAN Shuqin. Mining of core genes and analysis of related pathways in Alzheimer's disease based on bioinformatic analysis[J]. Journal of Clinical Medicine in Practice, 2024, 28(19): 22-26, 32. DOI: 10.7619/jcmp.20242038

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Mining of core genes and analysis of related pathways in Alzheimer's disease based on bioinformatic analysis

ZHANG Hong,
ZHAN Shuqin^,

Department of Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004

More Information

Received Date: May 15, 2024
Revised Date: July 18, 2024

Graphical Abstract

Abstract

Abstract

Objective
To identify core genes of Alzheimer's disease (AD) through bioinformatic analysis and explore potential pathogenic signaling pathways.
Methods
Gene expression profiling data related to AD were downloaded from the Gene Expression Omnibus (GEO) database, with datasets GSE227221 and GSE162873 selected for analysis. GEO2R online analysis software was applied to screen differentially expressed genes (DEGs) between AD tissue samples and normal brain tissue samples. The Disease Ontology (DO) enrichment analysis of DEGs was performed using the DOSE package in R software, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted through the online data analysis tool DAVID. Protein-protein interactions (PPI) among genes were analyzed using the STRING database, and a PPI network was constructed with Cytoscape software. Hub genes within the PPI network were identified and screened using the MCODE plugin. Based on MCODE scores, further analysis was conducted to select core genes.
Results
A total of 1, 373 DEGs with consistent expression trends involved in the onset and progression of AD were identified from the two datasets, with the core genes of GIMAP genes (including GIMAP1, GIMAP4, GIMAP5, GIMAP6, GIMAP7, and GIMAP1-GIMAP5). DO enrichment analysis revealed the strongest associations between DEGs and three diseases: systemic lupus erythematosus, lupus erythematosus, and atherosclerosis. GO functional enrichment analysis indicated that DEGs were primarily enriched in three signaling pathways: the classical Wnt signaling pathway, phospholipase C-activated G protein-coupled receptor pathway, and plasma membrane lateral domain pathway. KEGG pathway enrichment analysis showed that DEGs were primarily enriched in pathways such as cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and cancer-related transcriptional dysregulation.
Conclusion
The core pathogenic gene of AD may be the GIMAP gene, and the associated pathways are complex, potentially implicating immune dysfunction.
- Alzheimer's disease,
- bioinformatic analysis,
- immune dysfunction,
- gene expression database,
- enrichment analysis,
- signaling pathway

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References (25)

References

[1]	RAJESH Y, KANNEGANTI T D. Innate immune cell death in neuroinflammation and Alzheimer's disease[J]. Cells, 2022, 11(12): 1885. doi: 10.3390/cells11121885
[2]	SUN N, VICTOR M B, PARK Y P, et al. Human microglial state dynamics in Alzheimer's disease progression[J]. Cell, 2023, 186(20): 4386-4403. doi: 10.1016/j.cell.2023.08.037
[3]	HANNA R, FLAMIER A, BARABINO A, et al. G-quadruplexes originating from evolutionary conserved L1 elements interfere with neuronal gene expression in Alzheimer's disease[J]. Nat Commun, 2021, 12(1): 1828. doi: 10.1038/s41467-021-22129-9
[4]	CROUS-BOU M, MINGUILL&#XF; N C, GRAMUNT N, et al. Alzheimer's disease prevention: from risk factors to early intervention[J]. Alzheimers Res Ther, 2017, 9(1): 71. doi: 10.1186/s13195-017-0297-z
[5]	THIES W, BLEILER L. 2021 Alzheimer's disease facts and figures[J]. Alzheimers Dement, 2021, 17(3): 327-406. doi: 10.1002/alz.12328
[6]	LONG J M, HOLTZMAN D M. Alzheimer disease: an update on pathobiology and treatment strategies[J]. Cell, 2019, 179(2): 312-339. doi: 10.1016/j.cell.2019.09.001
[7]	PANZA F, LOZUPONE M, LOGROSCINO G, et al. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease[J]. Nat Rev Neurol, 2019, 15(2): 73-88. doi: 10.1038/s41582-018-0116-6
[8]	KRÜCKEN J, SCHROETEL R M, MÜLLER I U, et al. Comparative analysis of the human gimap gene cluster encoding a novel GTPase family[J]. Gene, 2004, 341: 291-304. doi: 10.1016/j.gene.2004.07.005
[9]	NITTA T, TAKAHAMA Y. The lymphocyte guard-IANs: regulation of lymphocyte survival by IAN/GIMAP family proteins[J]. Trends Immunol, 2007, 28(2): 58-65. doi: 10.1016/j.it.2006.12.002
[10]	NITTA T, NASREEN M, SEIKE T, et al. IAN family critically regulates survival and development of T lymphocytes[J]. PLoS Biol, 2006, 4(4): e103. doi: 10.1371/journal.pbio.0040103
[11]	GROSCH H. Subcortical dementia with pseudofocal motor disorders: mental deficiency in a 9-year old girl after whooping cough vaccination[J]. Dtsch Z Nervenheilkd, 1953, 170(3): 237-253. doi: 10.1007/BF00218543
[12]	SOLITARE G B. Neuronophagia[J]. Lancet, 1979, 1(8112): 387.
[13]	YE Y, GAO M Z, SHI W T, et al. The immunomodulatory effects of mesenchymal stem cell-derived extracellular vesicles in Alzheimer's disease[J]. Front Immunol, 2023, 14: 1325530.
[14]	KRÜCKEN J, SCHROETEL R M, MÜLLER I U, et al. Comparative analysis of the human gimap gene cluster encoding a novel GTPase family[J]. Gene, 2004, 341: 291-304. doi: 10.1016/j.gene.2004.07.005
[15]	ZENZ T, ROESSNER A, THOMAS A, et al. hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies[J]. Genes Immun, 2004, 5(2): 109-116. doi: 10.1038/sj.gene.6364044
[16]	BARNES M J, AKSOYLAR H, KREBS P, et al. Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice[J]. J Immunol, 2010, 184(7): 3743-3754. doi: 10.4049/jimmunol.0903164
[17]	SCHULTEIS R D, CHU H Y, DAI X Z, et al. Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5[J]. Blood, 2008, 112(13): 4905-4914. doi: 10.1182/blood-2008-03-146555
[18]	DATTA P, WEBB L M, AVDO I, et al. Survival of mature T cells in the periphery is intrinsically dependent on GIMAP1 in mice[J]. Eur J Immunol, 2017, 47(1): 84-93. doi: 10.1002/eji.201646599
[19]	WEBB L M, DATTA P, BELL S E, et al. GIMAP1 is essential for the survival of naive and activated B cells in vivo[J]. J Immunol, 2016, 196(1): 207-216. doi: 10.4049/jimmunol.1501582
[20]	SCHNELL S, DÉMOLLIōRE C, VAN DEN BERK P, et al. Gimap4 accelerates T-cell death[J]. Blood, 2006, 108(2): 591-599. doi: 10.1182/blood-2005-11-4616
[21]	HO C H, TSAI S F. Functional and biochemical characterization of a T cell-associated anti-apoptotic protein, GIMAP6[J]. J Biol Chem, 2017, 292(22): 9305-9319. doi: 10.1074/jbc.M116.768689
[22]	DAI P, RUAN P L, MAO Y, et al. Gimap5 promoted RSV degradation through interaction with M6PR[J]. J Med Virol, 2023, 95(1): e28390. doi: 10.1002/jmv.28390
[23]	XIE T H, LIU X, LI P. CD138 promotes the accumulation and activation of autoreactive T cells in autoimmune MRL/lpr mice[J]. Exp Ther Med, 2023, 26(6): 568. doi: 10.3892/etm.2023.12267
[24]	ZHANG M, LI J X, HUA C C, et al. Exploring an immune cells-related molecule in STEMI by bioinformatics analysis[J]. BMC Med Genomics, 2023, 16(1): 151. doi: 10.1186/s12920-023-01579-8
[25]	MARQUES E R M D C, HSIEH R, LOURENÇO S V, et al. Oral lupus erythematosus: Immunohistochemical evaluation of CD1a, CD21, CD123, and langerin expression in dendritic cells[J]. J Cutan Pathol, 2024, 51(5): 368-378. doi: 10.1111/cup.14568