title: Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy.
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.
authors: Molecular Pharmacology and Physiology Department, Byrd Alzheimer Institute, University of South Florida, Tampa, FL, USA. knash@health.usf.edu
authors: Kevin R
authors: KR
authors: Nash
authors: Daniel C
authors: DC
authors: Lee
authors: Jerry B
authors: JB
authors: Hunt
authors: Josh M
authors: JM
authors: Morganti
authors: Maj-Linda
authors: ML
authors: Selenica
authors: Peter
authors: P
authors: Moran
authors: Patrick
authors: P
authors: Reid
authors: Milene
authors: M
authors: Brownlow
authors: Clement
authors: C
authors: Guang-Yu Yang
authors: Miloni
authors: M
authors: Savalia
authors: Carmelina
authors: C
authors: Gemma
authors: Paula C
authors: PC
authors: Bickford
authors: Marcia N
authors: MN
authors: Gordon
authors: David
authors: D
authors: Morgan
mesh_terms: D000818:Animals; D054428:Chemokine CX3CL1 / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D024801:Tauopathies / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D016875:tau Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C558298:Mapt protein, mouse; D016875:tau Proteins