Absence of CX3CR1 impairs the internalization of Tau by microglia
Open accessAbstract
Extracellular Tau is toxic for neighboring cells, and it contributes to the progression of AD. The CX3CL1/CX3CR1 axis is an important neuron/microglia communication mechanism. We studied Tau clearance by microglia both in vitro (microglia primary cultures treated with Cy5-Tau, affinity chromatography to study the binding of Tau to CX3CR1, and Tau-CX3CL1 competition assays) and in vivo (stereotaxic injection of Cy5-Tau into WT and CX3CR1 −/− mice). The expression of CX3CR1, CX3CL1 and the microglial phagocytic phenotype were studied in brain tissue samples from AD patients. Tau binding to CX3CR1 triggers the internalization of the former by microglia, whereas S396 Tau phosphorylation decreases the binding affinity of this protein to CX3CR1. Of note, the progressive increase in the levels of phosho-Tau occurred in parallel with an increase in CX3CR1. In addition, our studies suggest that the phagocytic capacity of microglia in brain tissue samples from AD patients is decreased. Furthermore, the CX3CR1/CX3CL1 axis may be impaired in late stages of the disease. Our data suggest that the CX3CR1/CX3CL1 axis plays a key role in the phagocytosis of Tau by microglia in vitro and in vivo and that it is affected as AD progresses. Taken together, our results reveal CX3CR1 as a novel target for the clearance of extracellular Tau.
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CX3CR1 binds tau, and to a lesser extent hyperphosphorylated tau.
“CX3CR1 binds to tau, and to a lesser extent to hyperphosphorylated tau [263].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [263]
CX3CR1 deficiency impairs microglia-mediated tau internalization in vitro and promotes accumulation of hyperphosphorylated tau in vivo.
“CX3CR1 deficiency impairs microglia-mediated tau internalization in vitro, and promotes the accumulation of hyperphosphorylated tau in vivo [263, 429].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [263]
Microglia could phagocytize different tau species, and this process was partly dependent on the microglial fractalkine receptor CX3CR1.
“Microglia could phagocytize different tau species,386,387 and this process was partly dependent on microglial fractalkine receptor (CX3CR1) receptor.388”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [388]
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- Authors
- Bolós, M., Llorens-Martín, M., Perea, J. R., Jurado-Arjona, J., Rábano, A., Hernández, F., & Avila, J.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Fundacion Centro De Investigacion De Enfermedades Neurologicas (ES)
- Corresponding author
- Bolós, Marta
- Venue
- Molecular Neurodegeneration
- Published
- 2017-08-15
- Volume
- 12
- Issue
- 1
- Pages
- 59-59
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC5558740
- OpenAlex
- W2745518706
- Cited by
- 231
- References
- 46
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 27 · 2023: 32 · 2022: 31 · 2021: 36 · 2020: 23 · 2019: 20 · 2018: 11
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, public-domain)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Spanish Ministry of Health (SAF-2014-53040-P)
- The Alzheimer´s Association (2015-NIRG-340709)
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII
- Association for Frontotemporal Degeneration (US) (Basic Science Pilot Grant Award 2016)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- CX3CR1, fractalkine, microglia, tau clearance, Alzheimer's disease, microglial phagocytosis, neuron-microglia communication, extracellular tau, CX3CR1 knockout mice
- MeSH terms
- CX3C Chemokine Receptor 1, Alzheimer Disease, Animals, Brain, Neurons, Phosphorylation, tau Proteins, Microglia, Mice, Knockout
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