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.
|Number of pages||9|
|Journal||Neurobiology of Aging|
|State||Published - Jun 2013|
Bibliographical noteFunding Information:
The authors thank Dr Peter Mouton for his expert assistance with stereological counts. This work was funded in part by NIH/NIA R01 AG025509 , NIH NS76308 , and NIH AG15470 .
ASJC Scopus subject areas
- Neuroscience (all)
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology