Elevated BACE1 and IFNγ+ T Cells in Patients with Cognitive Impairment and the 5xFAD Mouse Model.

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.

Citation

Yaxi Zhan, Zuolong Chen, Shuxin Zheng, Linbin Dai, Wei Zhang, Yumeng Dai, Feng Gao, Yong Shen, Weiwei Zhang. Elevated BACE1 and IFNγ+ T Cells in Patients with Cognitive Impairment and the 5xFAD Mouse Model. ACS chemical neuroscience. 2025 Feb 05;16(3):384-392

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PMID: 39810314

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