Molecular intersections of traumatic brain injury and Alzheimer's disease: the role of ADMSC-derived exosomes and hub genes in microglial polarization.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Traumatic brain injury (TBI) is a significant contributor to global mortality and morbidity, with emerging evidence indicating a heightened risk of developing Alzheimer's disease (AD) following TBI. This study aimed to explore the molecular intersections between TBI and AD, focusing on the role of adipose mesenchymal stem cell (ADMSC)-derived exosomes and hub genes involved in microglial polarization. Transcriptome profiles from TBI (GSE58485) and AD (GSE74614) datasets were analyzed to identify differentially expressed genes (DEGs). The hub genes were validated in independent datasets (GSE180811 for TBI and GSE135999 for AD) and localized to specific cell types using single-cell RNA (scRNA) sequencing data (GSE160763 for TBI and GSE224398 for AD). Experimental validation was conducted to investigate the role of these genes in microglial polarization using cell culture and ADMSC-derived exosomes interventions. Our results identified three hub genes-Bst2, B2m, and Lgals3bp-that were upregulated in both TBI and AD, with strong associations to inflammation, neuronal apoptosis, and tissue repair processes. scRNA sequencing revealed that these genes are predominantly expressed in microglia, with increased expression during M1 polarization. Knockdown of these genes reduced M1 polarization and promoted M2 phenotype in microglia. Additionally, ADMSC-derived exosomes attenuated M1 polar

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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