SCRIB is a Shared Transcriptomic Biomarker Candidate Linking Cardioembolic Stroke and Alzheimer’s Disease

Abstract

Acute ischemic stroke is a major cause of death and disability, and post-stroke cognitive impairment remains a major clinical challenge. Cardioembolic stroke (CES), often associated with atrial fibrillation, is closely linked to cognitive decline. Increasing evidence suggests that vascular dysfunction contributes to both vascular cognitive impairment and Alzheimer’s disease (AD), but the shared molecular basis remains unclear. This study aimed to identify shared molecular signatures and candidate biomarkers linking CES and AD. Gene expression datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes were identified using limma, and disease-related gene modules were constructed using weighted gene co-expression network analysis. Functional enrichment analyses were performed to explore shared pathways. Three machine learning algorithms—LASSO, SVM-RFE, and random forest—were used to prioritize candidate genes. Receiver operating characteristic analysis, nomogram modeling, single-gene gene set enrichment analysis, and external validation were performed to evaluate the potential relevance of the identified gene. Seven overlapping genes were identified between CES and AD. Among them, SCRIB was consistently selected by the integrated feature-selection workflow and showed moderate diagnostic performance in both internal datasets. Supportive validation was observed in an independent AD dataset and in an atrial fibrillation-related surrogate validation cohort. SCRIB may represent a shared transcriptomic biomarker candidate linking CES and AD. These findings provide preliminary transcriptomic evidence for a potential molecular link between cerebrovascular pathology and neurodegeneration, but further mechanistic and clinical validation is required.