Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer’s Disease

Published on July 7, 2022

Imagine Alzheimer’s disease as a complex puzzle, with missing pieces that scientists are trying to find. One important piece of the puzzle is iron metabolism, which has been shown to be abnormal in people with Alzheimer’s. In this study, researchers searched for key genes related to iron metabolism that could help diagnose and treat Alzheimer’s. They looked at gene expression profiles and found nine hub genes that play a role in autophagy (a cellular cleaning process) and iron metabolism. These genes were used to create a diagnostic model for Alzheimer’s, and it performed well in blood samples. Interestingly, the researchers also discovered that these genes are linked to the immune system, suggesting their involvement in immune responses to Alzheimer’s. To top it off, they identified eight drugs that target these hub genes, potentially providing new treatments for Alzheimer’s and related conditions. This groundbreaking research could lead to better understanding of Alzheimer’s development and open up new possibilities for diagnosing and treating the disease. Ready to dive deeper? Check out the full article for more details!

Alzheimer’s disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.

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