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Updated: May 15, 2026
An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons
Published on: May 23, 2019
Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy
Kevin R Nash1, Daniel C Lee, Jerry B Hunt
1Molecular Pharmacology and Physiology Department, Byrd Alzheimer Institute, University of South Florida, Tampa, FL, USA. knash@health.usf.edu
Abstract:
Alzheimer's disease is characterized by amyloid plaques, neurofibrillary tangles, glial activation, and neurodegeneration. In mouse models, inflammatory activation of microglia accelerates tau pathology. The chemokine fractalkine serves as an endogenous neuronal modulator to quell microglial activation. Experiments with fractalkine receptor null mice suggest that fractalkine signaling diminishes tau pathology, but exacerbates amyloid pathology. Consistent with this outcome, we report here that soluble fractalkine overexpression using adeno-associated viral vectors significantly reduced tau pathology in the rTg4510 mouse model of tau deposition. Furthermore, this treatment reduced microglial activation and appeared to prevent neurodegeneration normally found in this model. However, in contrast to studies with fractalkine receptor null mice, parallel studies in an APP/PS1 model found no effect of increased fractalkine signaling on amyloid deposition. These data argue that agonism at fractalkine receptors might be an excellent target for therapeutic intervention in tauopathies, including those associated with amyloid deposition.
Insights
Overexpressing fractalkine reduced tau pathology and neurodegeneration in mouse models. This suggests targeting fractalkine receptors could be a promising therapy for tauopathies, including Alzheimer's disease.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Alzheimer's disease involves amyloid plaques, neurofibrillary tangles, and neuroinflammation.
- Microglial activation, driven by inflammation, worsens tau pathology in mouse models.
- Fractalkine is a chemokine that modulates neuronal activity and quells microglial activation.
Purpose of the Study:
- To investigate the therapeutic potential of fractalkine signaling in Alzheimer's disease models.
- To determine if increasing fractalkine levels can reduce tau pathology and neurodegeneration.
Main Methods:
- Adeno-associated viral vectors were used to overexpress soluble fractalkine in rTg4510 mice (tau deposition model).
- APP/PS1 mice (amyloid deposition model) were used for parallel studies.
- Microglial activation, tau pathology, and neurodegeneration were assessed.
Main Results:
- Soluble fractalkine overexpression significantly reduced tau pathology in rTg4510 mice.
- This treatment decreased microglial activation and prevented neurodegeneration.
- In contrast, increased fractalkine signaling did not affect amyloid deposition in APP/PS1 mice.
Conclusions:
- Targeting fractalkine receptors may be a viable therapeutic strategy for tauopathies.
- Fractalkine signaling demonstrates potential for treating neurodegenerative conditions characterized by tau pathology.
