2. Academic Validation
  3. Microbial infection instigates tau-related pathology in Alzheimer's disease via activating neuroimmune cGAS-STING pathway

Microbial infection instigates tau-related pathology in Alzheimer's disease via activating neuroimmune cGAS-STING pathway

  • Neuroscience. 2025 Mar 9:572:122-133. doi: 10.1016/j.neuroscience.2025.03.019.
Xiaoxu Yan 1,  Erlin Wang 2,  Meng Zhao 1,  Guanqin Ma 3,  Xiang-Xiong Xu 3,  Jie-Bin Zhao 3,  Xiaohong Li 3,  Jianxiong Zeng 4,  Xueling Ma 5
Affiliations

Affiliations

  • 1 Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
  • 2 Songjiang Research Institute, Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
  • 3 Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
  • 4 Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Songjiang Research Institute, Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China; Yunnan Key Laboratory of Biodiversity Information, Kunming, Yunnan 650201, China. Electronic address: zengjx@shsmu.edu.cn.
  • 5 Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. Electronic address: marlenexl@163.com.
PMID: 40064364 DOI: 10.1016/j.neuroscience.2025.03.019
Abstract

Microbial Infection, the strong trigger to directly induce inflammation in brain, is long considered a risk factor of Alzheimer's disease (AD), but how these infections contribute to neurodegeneration remains underexplored. To examine the effect of herpes simplex virus type 1 (HSV-1) Infection on tauopathy in local hippocampus of P301S mice, we utilized a modified HSV-1 strain (mHSV-1) potentially relevant to AD, we found that its Infection promotes tau-related pathology in part via activating neuroimmune cGAS-STING pathway in the tau mouse model. Specifically, STING ablation causes the detectable improvement of neuronal dysfunction and loss in P301S mice, which is causally linked to lowered proinflammatory status in the brain. Administration of STING Inhibitor H-151 alleviates neuroinflammation and tau-related pathology in P301S mice. These results jointly suggest that herpesviral Infection, as the vital environmental risk factor, could induce tau-related pathology in AD pathogenesis partially via neuroinflammatory cGAS-STING pathway.

Keywords

Alzheimer’s disease; Herpesvirus; Innate immunity; P301S mice; Tauopathy; cGAS-STING.

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