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Updated: Aug 21, 2026
An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons
Published on: May 23, 2019
Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein
Arianna Bellucci1, Andrew J Westwood, Esther Ingram
1Brain Repair Centre, University of Cambridge, Robinson Way, Cambridge CB2 2PY, UK.
Abstract:
Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant filaments made of hyperphosphorylated tau protein and neurodegeneration leading to nerve cell loss. At 5 months of age, the pathological changes are most marked in brainstem and spinal cord. Here we show that these changes are accompanied by marked neuroinflammation. Many tau-positive nerve cells in brainstem and spinal cord were strongly immunoreactive for interleukin-1beta and cyclooxygenase-2, indicating induction and overproduction of proinflammatory cytokines and enzymes. In parallel, numerous activated microglial cells were present throughout brain and spinal cord of transgenic mice, where they concentrated around tau-positive nerve cells. These findings suggest that inflammation may play a significant role in the events leading to neurodegeneration in the tauopathies and that anti-inflammatory compounds may have therapeutic potential.
Insights
Neuroinflammation, marked by interleukin-1beta and cyclooxygenase-2, accompanies tau pathology in transgenic mice. Activated microglia surround tau-positive neurons, suggesting inflammation
Area of Science:
- Neuroscience
- Pathology
- Immunology
Background:
- Human P301S tau protein transgenic mice model tauopathies.
- These mice exhibit hyperphosphorylated tau protein filaments and neurodegeneration.
Purpose of the Study:
- To investigate the role of neuroinflammation in P301S tau transgenic mice.
- To examine the relationship between tau pathology and inflammatory markers.
Main Methods:
- Analysis of tau-positive nerve cells for interleukin-1beta and cyclooxygenase-2 immunoreactivity.
- Assessment of microglial activation in the brain and spinal cord of transgenic mice.
Main Results:
- Significant neuroinflammation observed in P301S tau transgenic mice.
- Tau-positive neurons showed immunoreactivity for interleukin-1beta and cyclooxygenase-2.
- Activated microglia were abundant and concentrated around tau-positive neurons.
Conclusions:
- Neuroinflammation is a key feature accompanying tau pathology in this model.
- Interleukin-1beta and cyclooxygenase-2 are upregulated in affected neurons.
- Microglial activation suggests a role for inflammation in tau-induced neurodegeneration.
- Anti-inflammatory agents may offer therapeutic benefits for tauopathies.
