Affiliations: [a] Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| [b] Mental Health Research Center, Tehran Institute of Psychiatry – School of Behavioral Sciences and Mental Health, Iran University of Medical Sciences, Tehran, Iran
| [c] Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, USA
Correspondence:
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Correspondence to: Professor Ghasem Ahangari, Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, P.O. Box: 1497716316, Tehran, Iran. Tel.: +98 2144787384; Fax: +98 2144787399; E-mail: ghah@nigeb.ac.ir.
Abstract: Background:Late-onset Alzheimer’s disease (LOAD) is associated with many environmental and genetic factors. The effect of systemic inflammation on the pathogenesis of neurodegenerative diseases such as AD has been strongly suggested. T helper cells (Th) are one of the important components of the immune system and can easily infiltrate the brain in pathological conditions. The development of each Th-subset depends on the production of unique cytokines and their main regulator. Objective:This study aimed to compare the mRNA levels of Th-related genes derived from peripheral blood mononuclear cells of LOAD patients with control. Also, the identification of the most important Th1/Th2 genes and downstream pathways that may be involved in the pathogenesis of AD was followed by computational approaches. Methods:This study involved 30 patients with LOAD and 30 non-demented controls. The relative expression of T-cell cytokines (IFN-γ, TNF-α, IL-4, and IL-5) and transcription factors (T-bet and GATA-3) were assessed using Real-time PCR. Additionally, protein-protein interaction (PPI) was investigated by gene network construction. Results:A significant decrease at T-bet, IFN-γ, TNF-α, and GATA-3 mRNA levels was detected in the LOAD group, compared to the controls. However, there was no significant difference in IL-4 or IL-5 mRNA levels. Network analysis revealed a list of the highly connected protein (hubs) related to mitogen-activated protein kinase (MAPK) signaling and Th17 cell differentiation pathways. Conclusion:The findings point to a molecular dysregulation in Th-related genes, which can promising in the early diagnosis or targeted interventions of AD. Furthermore, the PPI analysis showed that upstream off-target stimulation may involve MAPK cascade activation and Th17 axis induction.
Keywords: Alzheimer’s disease, cytokine, gene expression, LOAD, mitogen-activated protein kinase, protein-protein interaction, T helper cell, Th17 cell, transcription factor
