Cuproptosis-related genes in natural killer cells of Alzheimer’s disease

doi:10.12307/2025.036

Abstract

Abstract: BACKGROUND: The immune-related pathogenesis of Alzheimer’s disease is still unclear. Exploring the correlation between natural killer cells and cuproptosis mechanism in Alzheimer’s disease patients through bioinformatics can provide a new direction for the study of the occurrence and development of Alzheimer’s disease.
OBJECTIVE: To screen the key genes related to cuproptosis of natural killer cells in peripheral blood of patients with Alzheimer’s disease by bioinformatics analysis and verify them in clinical specimens.
METHODS: The GEO online database was used to screen the transcriptome differentially expressed genes and natural killer cell related genes in the peripheral blood of patients with Alzheimer’s disease, and intersected with the reported cuproptosis factors. Differentially expressed cuproptosis-related genes were obtained. Then RT-qPCR technology was used to verify the relative gene expression levels. The experimental samples were all from peripheral blood of hospitalized patients in the Department of Neurology of Anhui Provincial Hospital from 2021 to 2023, and 30 patients in the disease group and 20 in the control group were included according to the inclusion and exclusion criteria. The protein-protein interaction network was further constructed using the online GeneMANIA website. R language was used for immune infiltration analysis. Transcription factor prediction was conducted based on ENCODE database.
RESULTS AND CONCLUSION: (1) The differential expression genes of peripheral blood transcriptome of Alzheimer’s disease patients in GSE63060 data set, natural killer cell related genes in GSE168522 data set, and reported cuproptosis genes were used to screen and obtain four differentially expressed cuproptosis-related genes by using online Venn diagram tool, LASSO algorithm, and random forest machine learning methods: ferredoxin 1 (FDX1), ATPase Cu2+ transporting alpha polypeptide (ATP7A), pyruvate dehydrogenase El subunit beta (PDHB), and dihydrolipoamide succinyltransferase (DLST). (2) Clinical sample experiments showed that FDX1 and ATP7A were up-regulated in peripheral blood of patients with Alzheimer’s disease (P < 0.001), and were differentially expressed in different genotypes of apolipoprotein E4 (P < 0.01, P < 0.001). The expression of PDHB and DLST in peripheral blood of patients with Alzheimer’s disease was down-regulated (P < 0.001), and there was no difference in apolipoprotein E4 genotypes (P > 0.05). (3) Protein-protein interaction network found that 20 functional proteins were associated with key genes, and immunoinfiltration analysis showed that key genes were significantly associated with 12 immune cells (P < 0.05 was considered to be relevant). (4) Bioinformatics analysis and experimental verification results suggest that FDX1, ATP7A, PDHB, and DLST are differentially expressed in Alzheimer’s disease, may participate in the occurrence and development of Alzheimer’s disease through the cuproptosis mechanism in peripheral blood natural killer cells, and also provide potential targets for the diagnosis and treatment of Alzheimer’s disease.

Key words: Alzheimer’s disease, bioinformatics, natural killer cell, cuproptosis, FDX1, ATP7A, PDHB, DLST

CLC Number:

Chen Guilin, Tang Qiqiang. Cuproptosis-related genes in natural killer cells of Alzheimer’s disease[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(19): 4172-4180.

Figures/Tables 7

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