Alterations in T-Cell Transcription Factors and Cytokine Gene Expression in Late-Onset Alzheimer's Disease.
J Alzheimers Dis
; 85(2): 645-665, 2022.
Article
em En
| MEDLINE
| ID: mdl-34864659
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucócitos Mononucleares
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Células Th17
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Doença de Alzheimer
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Irã