{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T20:15:55Z","timestamp":1780690555421,"version":"3.54.1"},"reference-count":136,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,1,18]]},"abstract":"<jats:p>Background: Late-onset Alzheimer\u2019s 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-\u03b3, TNF-\u03b1, 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-\u03b3, TNF-\u03b1, 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.<\/jats:p>","DOI":"10.3233\/jad-210480","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T16:43:21Z","timestamp":1638290601000},"page":"645-665","source":"Crossref","is-referenced-by-count":18,"title":["Alterations in T-Cell Transcription Factors and Cytokine Gene Expression in Late-Onset Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"85","author":[{"given":"Masoud","family":"Neshan","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Kazem","family":"Malakouti","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Tehran Institute of Psychiatry \u2013 School of Behavioral Sciences and Mental Health, Iran University of 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