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Published on: March 16, 2016
Elevated BACE1 and IFNγ+ T Cells in Patients with Cognitive Impairment and the 5xFAD Mouse Model
Yaxi Zhan1,2, Zuolong Chen2, Shuxin Zheng2
1Department of International Medical, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road 373, Hefei 230001, Anhui, China.
Abstract:
The dysregulation of T cell differentiation was associated with cognitive impairment. Recently, the peripheric β-secretase (BACE1) has been suggested as a regulator of T cell differentiation, which was increased in both cognitive impairment (CI) and type 2 diabetes mellitus (T2DM) in CI patients. However, the relationship between T cell dysfunction and CI remains unclear. To address this question, we measured T cell subtypes and BACE1 enzyme activity in a clinical cohort and 5xFAD mice. We found that both IFNγ+ Th1 and Tc1 cells were increased in the CI and T2DM-CI groups, which were associated with worsening cognitive function. The elevated IFNγ + Th1 and Tc1 cells were also observed in 8-month-old 5xFAD mice. The elevated BACE1-mediated INSR cleavage was associated with increased IFNγ + Th1 and Tc1 cells. These findings demonstrate the potential role of elevated BACE1 in IFNγ+ T cells and CI.

