Hub genes and diagnostic model associated with mitochondrial function in Alzheimer's disease

Background Alzheimer's disease (AD) represents the most prevalent neurodegenerative disorder, with mitochondrial dysfunction being observed in both AD patients and mouse models. Nonetheless, further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function. Methods In this study, the dataset GSE132903 was retrieved from the GEO database, encompassing both non‐demented (ND) control and AD samples. Through the combination of differential expression gene analysis, weighted gene co‐expression network analysis, and intersection with mitochondrial database gene sets, four hub genes associated with AD were identified. These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques. Results The hub genes identified through bioinformatics analysis include SYNJ2BP, VDAC1, NUBPL, and COX19. Within the GSE132903 dataset, the expression levels of SYNJ2BP, NUBPL, and COX19 were significantly elevated in the AD group compared to the non‐demented (ND) group, whereas VDAC1 expression was reduced in the AD group relative to the ND group. Furthermore, in the hippocampus of APP/PS1 and 5xFAD mouse models, the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results. Conclusion Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.