| First Author | Dai L | Year | 2021 |
| Journal | Brain Behav Immun | Volume | 98 |
| Pages | 337-348 | PubMed ID | 34500034 |
| Mgi Jnum | J:312957 | Mgi Id | MGI:6792469 |
| Doi | 10.1016/j.bbi.2021.08.234 | Citation | Dai L, et al. (2021) Elevated beta-secretase 1 expression mediates CD4(+) T cell dysfunction via PGE2 signalling in Alzheimer's disease. Brain Behav Immun 98:337-348 |
| abstractText | Circulating CD4(+) T cells are dysfunctional in Alzheimer's disease (AD), however, the underlying molecular mechanisms are not clear. In this study, we demonstrate that CD4(+) T cells from AD patients and 5xFAD transgenic mice exhibit elevated levels of beta-secretase 1 (BACE1). Overexpression of BACE1 in CD4(+) T cells potentiated CD4(+) T-cell activation and T-cell-dependent immune responses. Mechanistically, BACE1 modulates prostaglandin E2 (PGE2) synthetase-microsomal prostaglandin E synthase 2 (mPGES2)-to promote mPGES2 maturation and PGE2 production, which increases T-cell receptor (TCR) signalling. Moreover, administration of peripheral PGE2 signalling antagonists partially ameliorates CD4(+) T cell overactivation and AD pathology in 5xFAD mice. Overall, our results reveal a potential role for BACE1 in mediating CD4(+) T-cell dysfunction in AD. |
