Evidence map›Paper›PMID 40560886›Full record

ArticlePloS one2025

Novel insights from comprehensive analysis: The role of cuproptosis and peripheral immune infiltration in Alzheimer's disease.

Jing Wang, Zi-Wen Yu, Qi Liu, Jing-Xun Wu, Yi-Dan Zhang, Hui-Juan Wan, Min Bi, Nai-An Xiao, Kun-Mu Zheng, Bin Jiang

Abstract read
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Cuproptosis-associated genesFrontiers in immunology · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Jing WangDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.ORCID 0009-0008-1369-3500
Zi-Wen YuDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Qi LiuDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Jing-Xun WuDepartment of Medical Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Yi-Dan ZhangDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Hui-Juan WanDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Min BiDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Nai-An XiaoDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Kun-Mu ZhengDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Bin JiangDepartment of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCuproptosis is increasingly recognized as an essential factor in the pathological process of Alzheimer's disease (AD). However, the specific role of cuproptosis-related genes in AD remains poorly understood.

methodsOur first step was to obtain gene expression data from the GEO database and identify differentially expressed cuproptosis-associated genes (DECAGs) in AD. GO, KEGG, and GSEA analyses were then conducted on these genes. Subsequently, we attempted to classify AD patients by unsupervised clustering. Then, four machine-learning models were used to screen hub-genes from the DECAGs. We also explored the immune features of these genes and predicted target drugs. Molecular docking analysis was then performed on the predicted drugs and their corresponding hub-gene related proteins. Candidate markers were then validated by single-cell analysis and intracellular communication was investigated in a GEO scRNA-seq dataset. Lastly, we examined the expression levels of the hub-genes in peripheral blood cells using real-time quantitative PCR.

results19 DECAGs were found in AD and the key biological processes and molecular functions associated with AD were further determined. Two subtypes of peripheral blood cells showed significant alternations in AD: Cluster1 and Cluster2. Five hub-genes including FDX1, GLS, PDK1, MAP2K1, and SOD1 were then screened out from the machine-learning study. All of the five hub-genes were significantly correlated with various immunocytes. We discovered compounds targeting hub-gene related proteins and forecasted multiple strong hydrogen bonding interactions between the picked predicted drugs and the target proteins by molecular docking analysis. Subsequently, in the single-cell analysis of AD peripheral blood, all hub-genes except SOD1 were found to be up-regulated in B cells, NK cells, and CD4+ T cells, possibly acting on the MIF pathway. Finally, we discovered that the levels of PDK1 expression in AD patients were remarkably upregulated, while FDX1 and GLS were significantly decreased using qPCR.

conclusionThis study examined changes in intercellular communication between immune cells in the peripheral blood and identified five novel feature genes associated with cuproptosis in AD patients. These results facilitated a deeper understanding of the molecular mechanisms of AD and suggested novel therapeutic targets.

Indexed as

Alzheimer DiseaseGene Expression ProfilingHumansMolecular Docking Simulation

Identifiers

PMID40560886
PMCPMC12194219

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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.