Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis
Open accessAbstract
Alzheimer's disease (AD) is a neurodegenerative disease that primarily occurs in elderly individuals with cognitive impairment. Although extracellular β-amyloid (Aβ) accumulation and tau protein hyperphosphorylation are considered to be leading causes of AD, the molecular mechanism of AD remains unknown. Therefore, in this study, we aimed to explore potential biomarkers of AD. Next-generation sequencing (NGS) datasets, GSE173955 and GSE203206, were collected from the Gene Expression Omnibus (GEO) database. Analysis of differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein networks were performed to identify genes that are potentially associated with AD. Analysis of the DEG based protein-protein interaction (PPI) network using Cytoscape indicated that neuroinflammation and T-cell antigen receptor (TCR)-associated genes (LCK, ZAP70, and CD44) were the top three hub genes. Next, we validated these three hub genes in the AD database and utilized two machine learning models from different AD datasets (GSE15222) to observe their general relationship with AD. Analysis using the random forest classifier indicated that accuracy (78%) observed using the top three genes as inputs differed only slightly from that (84%) observed using all genes as inputs. Furthermore, another data set, GSE97760, which was analyzed using our novel eigenvalue decomposition method, indicated that the top three hub genes may be involved in tauopathies associated with AD, rather than Aβ pathology. In addition, protein-protein docking simulation revealed that the top hub genes could form stable binding sites with acetylcholinesterase (ACHE). This suggests a potential interaction between hub genes and ACHE, which plays an essential role in the development of anti-AD drug design. Overall, the findings of this study, which systematically analyzed several AD datasets, illustrated that LCK, ZAP70, and CD44 may be used as AD biomarkers. We also established a robust prediction model for classifying patients with AD.
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The 832 LOAD spheroid DEGs overlap with bulk RNA-seq datasets from various brain regions in individuals with AD, GO terms related to apoptosis/neurodegeneration, and AD risk genes from Alzgene database, with overlaps ranging from 8 to 135 genes.
“We further compared 832 DEGs with bulk RNA-seq datasets from various brain regions in individuals with AD (80–84), gene members in GO terms related to apoptosis/neurodegeneration, and AD risk genes from Alzgene database, revealing distinct sets of DEGs with overlaps ranging from 8 to 135 genes (Table S7, page 2, 3 and 4).”
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Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming
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- Authors
- Guo, W., Gou, X., Yu, L., Zhang, Q., Yang, P., Pang, M., Pang, X., Pang, C., Wei, Y., & Zhang, X.
- Affiliations
- Sichuan Normal University (CN)
- Chengdu University of Technology (CN)
- Sichuan University (CN)
- University of Electronic Science and Technology of China (CN)
- Corresponding author
- Wei, Yanyu
- Zhang, XiaoYu
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2023-03-28
- Volume
- 14
- Pages
- 1129470-1129470
- ISSN
- 1664-2295 (ISSN-L)
- PMC
- PMC10086260
- OpenAlex
- W4361217308
- Cited by
- 10
- References
- 71
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Update notices
- corrigendum (2023-04-26)
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (61988102)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, MAPT, acetylcholinesterase, Lck, ZAP-70, CD44, neuroinflammation, tauopathy, biomarkers, differential gene expression, protein-protein interaction network, hub genes, random forest classification, protein-protein docking
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