Identification of m5C-associated gene signatures in Alzheimer's disease and their relationship with immune infiltration.
- 1Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
- 2Department of Clinical Psychology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
- 3Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, China.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex genetic, epigenetic, and immune components. This study investigated m5C-associated gene-expression signatures in AD and explored their biological and immune-cell associations. Two GEO datasets (GSE132903 and GSE118553) were used for discovery, with GSE33000 and GSE122063 used for external expression assessment. Differential-expression, GO/KEGG enrichment, GSEA, protein-protein interaction, regulatory-network, CIBERSORTx, and ROC analyses were performed. Selected candidates were further examined by RT-qPCR in cortex and hippocampus from 4-month-old male 5 ×FAD mice and age-matched WT controls (n = 5 per group). Five m5C-associated differentially expressed candidate genes (ZBTB4, MBD4, ZBTB33, NEIL1, and TDG) were identified. ZBTB4 showed reproducible expression differences across several human datasets, but its ROC AUC values (0.657, 0.605, and 0.569) indicated limited standalone discriminatory performance. Gene-immune-cell correlations were statistically significant but weak. In the 5 ×FAD model, Zbtb4 and Mbd4 mRNA levels were significantly reduced in both cortex and hippocampus compared with WT controls. The integrated analyses identify candidate methylation/m5C-associated expression changes in AD and provide in vivo transcript-level corroboration for Zbtb4 and Mbd4. The ROC and immune-infiltration findings should be considered exploratory and do not establish clinical diagnostic utility or causal immune mechanisms.
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BibTeX
@article{ai2026identification,
title = {{Identification of m5C-associated gene signatures in Alzheimer's disease and their relationship with immune infiltration.}},
author = {Pan Ai and Xuyang Wang and Hui Shi and Anshi Wu and Jing Wang},
journal = {IBRO neuroscience reports},
year = {2026},
month = oct,
doi = {10.1016/j.ibneur.2026.10.008},
url = {https://europepmc.org/article/MED/42999580},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Identification of m5C-associated gene signatures in Alzheimer's disease and their relationship with immune infiltration.
AU - Pan Ai
AU - Xuyang Wang
AU - Hui Shi
AU - Anshi Wu
AU - Jing Wang
PY - 2026
DA - 2026/10/17
JO - IBRO neuroscience reports
DO - 10.1016/j.ibneur.2026.10.008
UR - https://europepmc.org/article/MED/42999580
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex genetic, epigenetic, and immune components. This study investigated m5C-associated gene-expression signatures in AD and explored their biological and immune-cell associations. Two GEO datasets (GSE132903 and GSE118553) were used for discovery, with GSE33000 and GSE122063 used for external expression assessment. Differential-expression, GO/KEGG enrichment, GSEA, protein-protein interaction, regulatory-network, CIBERSORTx, and ROC analyses were performed. Selected candidates were further examined by RT-qPCR in cortex and hippocampus from 4-month-old male 5 ×FAD mice and age-matched WT controls (n = 5 per group). Five m5C-associated differentially expressed candidate genes (ZBTB4, MBD4, ZBTB33, NEIL1, and TDG) were identified. ZBTB4 showed reproducible expression differences across several human datasets, but its ROC AUC values (0.657, 0.605, and 0.569) indicated limited standalone discriminatory performance. Gene-immune-cell correlations were statistically significant but weak. In the 5 ×FAD model, Zbtb4 and Mbd4 mRNA levels were significantly reduced in both cortex and hippocampus compared with WT controls. The integrated analyses identify candidate methylation/m5C-associated expression changes in AD and provide in vivo transcript-level corroboration for Zbtb4 and Mbd4. The ROC and immune-infiltration findings should be considered exploratory and do not establish clinical diagnostic utility or causal immune mechanisms.
SN - 2667-2421
ER -