Evidence map›Paper›PMID 42897366›Full record

ArticleMolecular neurobiology2026

Identification of Succinylation-Related Transcriptional Signatures in Alzheimer's Disease: Integrated Bioinformatics Analysis and Clinical Validation.

Yuanyuan Cheng, Yue Pu, Hong Chen, Ying Ma, Chuanbing Huang, Juan Zhang

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Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

6 authors.

Yuanyuan Cheng *Anhui University of Chinese Medicine, Hefei, Anhui Province, 230031, China.ORCID http://orcid.org/0009-0002-3484-5610
Yue Pu *Anhui University of Chinese Medicine, Hefei, Anhui Province, 230031, China.ORCID http://orcid.org/0000-0002-2670-1863
Hong ChenAnhui University of Chinese Medicine, Hefei, Anhui Province, 230031, China.ORCID http://orcid.org/0000-0002-9026-9112
Ying MaAnhui University of Chinese Medicine, Hefei, Anhui Province, 230031, China.ORCID http://orcid.org/0009-0006-3040-1931
Chuanbing HuangFirst Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, 230038, China.ORCID http://orcid.org/0009-0007-9163-1754
Juan ZhangFirst Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, 230038, China. juanzhangz@163.com.ORCID http://orcid.org/0000-0003-4673-3448

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder involving mitochondrial dysfunction, oxidative stress, proteostasis imbalance, and immune-inflammatory alterations. Protein succinylation is closely linked to mitochondrial metabolic status, but peripheral blood transcriptomic signatures related to succinylation in AD remain insufficiently characterized. This study aimed to identify peripheral blood transcriptional candidate biomarkers associated with a predefined succinylation-related gene set in AD. The GSE63061 dataset was used as the discovery cohort, and GSE63060 served as an external validation cohort. Differential expression analysis, ssGSEA-derived succinylation scoring, and WGCNA were integrated with a predefined succinylation-related gene set. Candidate biomarkers were then refined through four feature selection approaches: LASSO, random forest, SVM-RFE, and Boruta, and their discriminatory performance was evaluated by ROC analysis, nomogram construction, calibration analysis, decision curve analysis, and SHAP analysis. Functional enrichment, GSVA/GSEA, GeneMANIA, immune-cell signature analysis, and single-cell analyses were used to explore biological relevance and cellular distribution. qRT-PCR was performed using peripheral blood-derived PBMC samples for experimental validation. Five genes, NDUFA1, NDUFS5, RPS27A, AIF1, and PRDX1, were identified as candidate biomarkers associated with a succinylation-related transcriptional signature in AD. These genes were mainly involved in mitochondrial complex I activity, oxidative phosphorylation, ribosomal function, protein homeostasis, redox balance, and immune inflammation. Immune-cell signatures and single-cell analyses further suggested that the signature was associated with T cells, B cells, NK cells, and monocytes/macrophages. qRT-PCR confirmed significant downregulation of all five genes in AD PBMC samples (P < 0.05). These findings suggest that peripheral blood transcriptional signatures associated with succinylation-related genes may provide candidate biomarkers and hypothesis-generating clues for AD.

Indexed as

Alzheimer DiseaseComputational BiologySuccinic AcidTranscriptomeBiomarkersGene Expression ProfilingHumansReproducibility of ResultsBiomarkersSuccinic AcidAlzheimer’s diseaseBiomarkerMachine learningSuccinylation

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.