Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease
Background: Synaptic dysfunction and synapse loss occur in Alzheimer's disease (AD). The current study aimed to identify synaptic-related genes with diagnostic potential for AD. Methods: Differentially expressed genes (DEGs) were overlapped with phenotype-associated module selected through weig...
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Elsevier
2025-06-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825001220 |
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| author | Huijun Li Yawei Fan Chan Chen Yuzhong Xu Xiong Wang Wei Liu |
| author_facet | Huijun Li Yawei Fan Chan Chen Yuzhong Xu Xiong Wang Wei Liu |
| author_sort | Huijun Li |
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| description | Background: Synaptic dysfunction and synapse loss occur in Alzheimer's disease (AD). The current study aimed to identify synaptic-related genes with diagnostic potential for AD. Methods: Differentially expressed genes (DEGs) were overlapped with phenotype-associated module selected through weighted gene co-expression network analysis (WGCNA), and synaptic-related genes. The overlapped hub genes were further processed using machine learning algorithms, intersected with module gene from protein-protein interaction (PPI) network constructed with DEGs, to yield co-hub genes. The diagnostic potentials of the co-hub genes were examined by receiver operating characteristic (ROC) analysis. Correlation between co-hub genes with clinical features and immune cell infiltration was analyzed. Finally, the expression of co-hub genes was analyzed in several datasets and validated in AD transgenic mice. Results: A total of three co-hub genes were identified, including MAP1B, L1CAM, and GABBR2. GABBR2 showed area under the curve (AUC) values of 0.98, 0.81, and 0.88 in the training and two external validation datasets. GABBR2 was negatively correlate with beta- and gamma-secretase activities, and infiltration of natural killer T cells and effector memory CD8 T cells. Finally, GABBR2 was validated to be downregulated in AD transgenic mice, aligning with bioinformatic findings. GABBR2 overexpression in N2a/APP cells increased ADAM10 while decreased of BACE1, leading to upregulation of sAPPα while downregulation of sAPPβ. Conclusion: In conclusion, GABBR2 acts as a novel biomarker for the diagnosis of AD and negatively correlated with Aβ in AD. |
| format | Article |
| id | doaj-art-91e2eb1e4cb64a6da462d3bebb1d7ddf |
| institution | OA Journals |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-91e2eb1e4cb64a6da462d3bebb1d7ddf2025-08-20T02:37:46ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210203510.1016/j.bbrep.2025.102035Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's diseaseHuijun Li0Yawei Fan1Chan Chen2Yuzhong Xu3Xiong Wang4Wei Liu5Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaDepartment of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaThe Baoan People's Hospital of Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen, 518101, ChinaThe Baoan People's Hospital of Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen, 518101, China; Corresponding author.Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Corresponding author.Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Corresponding author.Background: Synaptic dysfunction and synapse loss occur in Alzheimer's disease (AD). The current study aimed to identify synaptic-related genes with diagnostic potential for AD. Methods: Differentially expressed genes (DEGs) were overlapped with phenotype-associated module selected through weighted gene co-expression network analysis (WGCNA), and synaptic-related genes. The overlapped hub genes were further processed using machine learning algorithms, intersected with module gene from protein-protein interaction (PPI) network constructed with DEGs, to yield co-hub genes. The diagnostic potentials of the co-hub genes were examined by receiver operating characteristic (ROC) analysis. Correlation between co-hub genes with clinical features and immune cell infiltration was analyzed. Finally, the expression of co-hub genes was analyzed in several datasets and validated in AD transgenic mice. Results: A total of three co-hub genes were identified, including MAP1B, L1CAM, and GABBR2. GABBR2 showed area under the curve (AUC) values of 0.98, 0.81, and 0.88 in the training and two external validation datasets. GABBR2 was negatively correlate with beta- and gamma-secretase activities, and infiltration of natural killer T cells and effector memory CD8 T cells. Finally, GABBR2 was validated to be downregulated in AD transgenic mice, aligning with bioinformatic findings. GABBR2 overexpression in N2a/APP cells increased ADAM10 while decreased of BACE1, leading to upregulation of sAPPα while downregulation of sAPPβ. Conclusion: In conclusion, GABBR2 acts as a novel biomarker for the diagnosis of AD and negatively correlated with Aβ in AD.http://www.sciencedirect.com/science/article/pii/S2405580825001220Alzheimer's diseaseGABBR2DiagnosisImmune cell infiltration |
| spellingShingle | Huijun Li Yawei Fan Chan Chen Yuzhong Xu Xiong Wang Wei Liu Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease Biochemistry and Biophysics Reports Alzheimer's disease GABBR2 Diagnosis Immune cell infiltration |
| title | Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease |
| title_full | Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease |
| title_fullStr | Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease |
| title_full_unstemmed | Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease |
| title_short | Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease |
| title_sort | identification of gabbr2 as a diagnostic marker and its association with aβ in alzheimer s disease |
| topic | Alzheimer's disease GABBR2 Diagnosis Immune cell infiltration |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825001220 |
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