Common biomarkers of Alzheimer disease and postoperative delirium
Clinical Snapshot
PICO Framework
| P — Population | Patients with Alzheimer disease and postoperative delirium from gene expression datasets |
| I — Intervention | Gene expression profiling and bioinformatics analysis |
| C — Comparator | Healthy controls without AD or POD |
| O — Outcomes | Identification of common differentially expressed genes and potential biomarkers (BTK, NCF2, CRH, FCGR3A, SERPINA3) |
Bottom Line
This bioinformatics study identified 23 shared genes between Alzheimer disease and postoperative delirium, with BTK and NCF2 emerging as key biomarkers. While the computational approach is methodologically sound and suggests common pathophysiological pathways involving neuroinflammation and immune dysfunction, the findings require experimental validation and clinical correlation. The identification of shared biomarkers supports the hypothesis that POD and AD may have overlapping mechanisms, potentially informing risk stratification and prevention strategies. However, clinicians should await validation studies before considering these biomarkers for clinical decision-making. The work provides valuable foundation for future research into the relationship between perioperative cognitive complications and neurodegenerative disease, particularly relevant given Australia's aging surgical population.
Key Findings
P Value: Not specified for individual biomarkers
Effect Size: 259 DEGs in POD (148 up-regulated, 111 down-regulated) and 199 DEGs in AD (25 up-regulated, 174 down-regulated)
Primary Outcome: Identification of 23 common differentially expressed genes between AD and POD
Nnt Or Sensitivity: BTK and NCF2 identified as sufficient to distinguish patients from controls using decision tree analysis
Confidence Interval: Not reported
Clinical Application
Requires development of clinical-grade assays for identified biomarkers before practical implementation Relevant to Australian perioperative care given aging population and POD prevention focus in ANZCA guidelines, though TGA approval would be needed for any diagnostic applications Patients at risk for postoperative delirium, particularly those with underlying cognitive impairment or AD risk factors
Abstract
Alzheimer disease (AD) and Postoperative delirium (POD) may share a common mechanism, but their shared genes and potential novel therapeutic targets remains unknown. We selected datasets GSE48350, GSE4226, and GSE16759 containing AD and control samples from the GEO database for AD model development, and use the GSE63061 dataset for AD model validation. The GSE163943 dataset containing PODs and controls was used to identify common genes. Differentially expressed genes (DEGs) associated with POD and AD respectively, as well as common DEGs between 2 diseases were analyzed. Shared DEGs were assessed using gene ontology and KEGG enrichment and PPI interaction networks. Machine learning algorithms, nomogram and decision tree analyses were used to interpret top 5 genes and visualize the models. 259 DEGs in POD with 148 being up-regulated and 111 down-regulated, and 199 DEGs in AD with 25 up-regulated and 174 down-regulated were found, of which 23 were common to POD and AD. Gene ontology analysis indicated that DEGs were primarily concentrated in 9 distinct biological processes, while KEGG results revealed 3 major metabolic pathways. Five hub genes emerged as potential diagnostic biomarkers for both diseases, Bruton tyrosine kinase (BTK), NCF2, CRH, FCGR3A, and SERPINA3. The LASSO model determined that the 23 common genes could serve as biomarkers for both POD and AD patients, and the Random Forest model is the the most suitable model. POD or AD decision trees showed BTK and NCF2 were sufficient to distinguish between POD or AD patients and healthy controls. BTK and NCF2 were identified common biomarkers of POD and AD. Further investigations are required to verify correlations between gene expression levels and pathological characteristics.
References
- 1.Fang, Y., Zhang, X., & Zhan, G. (2026). Common biomarkers of Alzheimer disease and postoperative delirium. Medicine, 105(22), e48921. https://doi.org/10.1097/MD.0000000000048921
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