Unraveling the Puzzle of Dementia: Genes and Neuroinflammation

Published on October 26, 2022

Imagine solving a complex puzzle that could reveal the key to understanding dementia. In this study, scientists examined the influence of cytokine gene polymorphisms on the risk of developing dementia. Cytokines, such as interleukin (IL)-α, IL-6, tumor necrosis factor (TNFα), and interferon-gamma (IFN-γ), play a crucial role in neuroinflammation, a process believed to contribute to certain types of dementia. By analyzing genetic data from 221 dementia patients and 710 controls, the researchers applied a clever statistical technique called multifactor dimensionality reduction (MDR) analysis to identify synergistic interactions between specific gene variants. The best prediction model included the genes TNFα, IFNγ, IL1α, and IL6, and it successfully identified individuals at risk for dementia with a whopping 72% accuracy! These findings suggest that genetic interactions are an important piece of the dementia puzzle and can help identify vulnerable populations.

ObjectiveEvidence supports the important role of neuroinflammation in some types of dementia. This study aimed to evaluate the effect of epistasis of gene cytokines such as interleukin (IL)-α, IL-6, tumor necrosis factor (TNFα), and interferon-gamma (IFN-γ) on the susceptibility to the development of dementia.Materials and methodsIn the study, 221 patients diagnosed with dementia and 710 controls were included. The multifactor-dimensionality reduction (MDR) analysis was performed to identify the epistasis between SNP located in genes of IL-α (rs1800587), IL-6 (rs1800796), TNFα (rs361525 and rs1800629), and IFNγ (rs2069705). The best risk prediction model was identified based on precision and cross-validation consistency.ResultsMultifactor-dimensionality reduction analysis detected a significant model with the genes TNFα, IFNγ, IL1α, and IL6 (prediction success: 72%, p < 0.0001). When risk factors were analyzed with these polymorphisms, the model achieved a similar prediction for dementia as the genes-only model.ConclusionThese data indicate that gene–gene interactions form significant models to identify populations susceptible to dementia.

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