TBX21, the Master regulator of the type 1 immune response, overexpresses in the leukocytes of peripheral blood in patients with late-onset Alzheimer’s disease

Abstract

Abstract Background The involvement of the peripheral immune system in the etiology of neurodegenerative diseases has recently been emphasized. Genome-wide association studies (GWAS) have recently identified several candidate immune genes linked to development of both Alzheimer’s disease (AD) and depression. TBX21 (T-bet) which drives the Th1 immune response, is linked to the major depressive disorder (MDD) phenotype. This study investigated the association between the TBX21 immune gene and the possibility of late-onset Alzheimer’s disease (LOAD) incidence in 194 LOAD and 200 control subjects using the real-time qPCR and the Tetra-ARMS-PCR methods. We also used an in silico approach to analyze the potential effects imparted by TBX21 rs17244587 and rs41515744 polymorphisms in LOAD pathogenesis. Results We found that the TBX21 “immune gene” had significantly elevated mRNA expression levels in the leukocytes of peripheral blood in patients with LOAD (P < 0.0001). We also found an upward trend in TBX21 expression with increasing age in LOAD patients compared to the control group (P < 0.05; CI = 95%). We noticed that the TT genotype of rs41515744 plays a protective role in LOAD incidence, as it attenuates the expression of TBX21 in the control group. We observed that the dominant model of rs41515744 represented a substantial association with LOAD (P = 0.019). Conclusions Our results show for the first time the likely impact of the TBX21 (T-bet) immune gene in LOAD development and that the elevated TBX21 mRNAs in the WBCs of LOAD patients may represent a new easy diagnostic test for Alzheimer’s disease.

Keywords

• TBX21 (T-bet)
• Peripheral immunity
• Late-Onset Alzheimer’s Disease (LOAD)
• Major Depressive Disorder (MDD)
• Expression