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Updated: May 23, 2025
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
Microbial infection instigates tau-related pathology in Alzheimer's disease via activating neuroimmune cGAS-STING
Xiaoxu Yan1, Erlin Wang2, Meng Zhao1
1Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
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.
Insights
Herpes simplex virus type 1 (HSV-1) infection can worsen Alzheimer's disease (AD) by activating the brain's cGAS-STING inflammatory pathway. Blocking this pathway improves neuronal function and reduces tau pathology in mouse models.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Microbial infections are linked to Alzheimer's disease (AD) pathogenesis.
- The precise mechanisms by which infections contribute to neurodegeneration are not fully understood.
- Herpes simplex virus type 1 (HSV-1) is a potential environmental risk factor for AD.
Purpose of the Study:
- To investigate the impact of modified HSV-1 (mHSV-1) infection on tauopathy in the hippocampus of P301S mice.
- To elucidate the role of the cGAS-STING neuroinflammatory pathway in HSV-1-induced tau pathology.
Main Methods:
- Utilized a modified HSV-1 strain (mHSV-1) in P301S tau mouse models.
- Examined the effects of Sting gene ablation on neuronal function and loss.
- Administered the STING inhibitor H-151 to assess its impact on neuroinflammation and tau pathology.
Main Results:
- HSV-1 infection promotes tau-related pathology in the hippocampus of P301S mice.
- Sting ablation significantly improved neuronal dysfunction and loss, correlating with reduced brain inflammation.
- H-151 treatment alleviated neuroinflammation and tau pathology in the P301S mouse model.
Conclusions:
- Herpesviral infection can induce tau-related pathology in AD pathogenesis.
- The neuroinflammatory cGAS-STING pathway is a key mediator in this process.
- Targeting the cGAS-STING pathway offers a potential therapeutic strategy for AD linked to viral infections.
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