The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
CX3CR1 Protein Signaling Modulates Microglial Activation and Protects against Plaque-independent Cognitive Deficits in a Mouse Model of Alzheimer Disease
Open accessAbstract
Aberrant microglial activation has been proposed to contribute to the cognitive decline in Alzheimer disease (AD), but the underlying molecular mechanisms remain enigmatic. Fractalkine signaling, a pathway mediating the communication between microglia and neurons, is deficient in AD brains and down-regulated by amyloid-β. Although fractalkine receptor (CX3CR1) on microglia was found to regulate plaque load, no functional effects have been reported. Our study demonstrates that CX3CR1 deficiency worsens the AD-related neuronal and behavioral deficits. The effects were associated with cytokine production but not with plaque deposition. Ablation of CX3CR1 in mice overexpressing human amyloid precursor protein enhanced Tau pathology and exacerbated the depletion of calbindin in the dentate gyrus. The levels of calbindin in the dentate gyrus correlated negatively with those of tumor necrosis factor α and interleukin 6, suggesting neurotoxic effects of inflammatory factors. Functionally, removing CX3CR1 in human amyloid precursor protein mice worsened the memory retention in passive avoidance and novel object recognition tests, and their memory loss in the novel object recognition test is associated with high levels of interleukin 6. Our findings identify CX3CR1 as a key microglial pathway in protecting against AD-related cognitive deficits that are associated with aberrant microglial activation and elevated inflammatory cytokines.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“However, such complete deletion has also been associated with worsening memory deficits and tau pathology (28–31).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208
Initiative, T. A. D. N., Hollingworth, P., CHARGE consortium, EADI1 consortium, Harold, D., Sims, R., Gerrish, A., Lambert, J.-C., Carrasquillo, M. M., Abraham, R., et al. (2011) · Nature Genetics · doi:10.1038/ng.803 · Cited by 1,997
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858
Self-citationMucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856
Recognition memory: What are the roles of the perirhinal cortex and hippocampus?
Brown, M. W., & Aggleton, J. P. (2001) · Nature reviews. Neuroscience · doi:10.1038/35049064 · Cited by 1,624
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531
Self-citationSoluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease
Lue, L.-F., Kuo, Y.-M., Roher, A. E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J. H., Rydel, R. E., & Rogers, J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65184-x · Cited by 1,530
Imai, T., Hieshima, K., Haskell, C. A., Baba, M., Nagira, M., Nishimura, M., Kakizaki, M., Takagi, S., Nomiyama, H., Schall, T. J., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80438-9 · Cited by 1,472
Flagged first, then by citations
Research works printed but not linked: 1
- Wyss-Coray, 2006, Nat. Med., 12, 1005
Cited by
Sorted by citations
Items 201–268 of 268
Ageing-related changes in the regulation of microglia and their interaction with neurons
Rommy von Bernhardi, M., & Eugenín, J. L. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110241 · Cited by 10
Pourhadi, M., Zali, H., Ghasemi, R., & Vafaei‐Nezhad, S. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02951-y · Cited by 10
Headmasters: Microglial regulation of learning and memory in health and disease
Weinhard, L., d’Errico, P., & Tay, T. L. (2018) · AIMS molecular science · doi:10.3934/molsci.2018.1.63 · Cited by 11
Short term exposure to ethyl pyruvate has long term anti-inflammatory effects on microglial cells
Stanisavljević, S., Jevtić, B., Djedović, N., & Miljković, D. M. (2015) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2015.03.006 · Cited by 9
Cell ageing: a flourishing field for neurodegenerative diseases
Brites, D. M. T. O. (2015) · AIMS molecular science · doi:10.3934/molsci.2015.3.225 · Cited by 10
Ono, T., & Kuhara, S. (2014) · BMC Bioinformatics · doi:10.1186/1471-2105-15-179 · Cited by 8
Grubman, A., Choo, X. Y., Chew, G., Ouyang, J. F., Sun, G., Croft, N. P., Rossello, F. J., Simmons, R., Buckberry, S., Landin, D. V., et al. (2019) · doi:10.1101/639054 · Cited by 7
Hexokinase and Glycolysis: Between Brain Cells Life and Death
da Mata, L. R. S., Santos, L., & César, M. C. (2023) · Current Chemical Biology · doi:10.2174/2212796817666230510095530 · Cited by 7
Advances in the multifunctional roles of CX3CL1 in the central nervous system
Chen, Y., Liu, J., Zhang, S., Gao, M., Wang, F., Cai, M., Lu, C., Li, S. A., & Zhao, J. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1696689 · Cited by 7
Goode‐Romero, G., & Domı́nguez, L. (2022) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2022.108278 · Cited by 7
Bivona, G., Sammataro, S., & Ghersi, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147893 · Cited by 7
Alpha-1 antitrypsin inhibits fractalkine-mediated monocyte-lung endothelial cell interactions
Mikosz, A. M., Ni, K., Gally, F., Pratte, K., Winfree, S., Lin, Q., Echelman, I., Wetmore, B., Cao, D., Justice, M. J., et al. (2023) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00023.2023 · Cited by 6
Fractalkine signaling in regulation of insulin secretion
Gregg, B. E., Lumeng, C. N.-K., & Bernal‐Mizrachi, E. (2014) · Islets · doi:10.4161/isl.27861 · Cited by 6
Chang, Y., Zheng, X., Wang, M., Zhang, Q., Gao, Y., Wang, Y., Sun, Y., Fan, H., Li, X., Du, L.-D., et al. (2026) · Phytotherapy Research · doi:10.1002/ptr.70177 · Cited by 5
Wen, C., Kang, H., & Chan, J. Y. H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312575 · Cited by 5
The Amyloid-beta rich CNS environment alters myeloid cell functionality independent of their origin
Drost, N., Houtman, J., Cseresnyés, Z., Niesner, R. A., Rinnenthal, J.-L., Miller, K. R., Prokop, S., & Heppner, F. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-63989-3 · Cited by 5
Polymerization of misfolded Z alpha-1 antitrypsin protein lowers CX3CR1 expression in human PBMCs
Tumpara, S., Ballmaier, M., Wrenger, S., König, M., Lehmann, M., Lichtinghagen, R., Martínez–Delgado, B., Korenbaum, E., DeLuca, D. S., Jedicke, N., et al. (2021) · eLife · doi:10.7554/elife.64881 · Cited by 5
Targeting chemokine signaling networks for therapeutics in skeletal disorders
Gao, W., Gao, Z., Chen, Y., Wang, Y., Li, Y., Qian, Y., Lu, H., Ling, X., Xiao, H., Yang, P., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1667440 · Cited by 4
Aging Microglia and Their Impact in the Nervous System
Rommy von Bernhardi, M., & Eugenín, J. L. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_21 · Cited by 4
Aubert, A., Stüder, F., Colombo, B. M., & Mendoza-Parra, M. A. (2021) · Brain Sciences · doi:10.3390/brainsci11101338 · Cited by 4
Li, R., Zhang, J., Fan, J.-Q., & Lin, B. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03692-8 · Cited by 3
Lv, J., Shen, X., Shen, X.-Y., Li, X., Jin, Z.-Y., Ouyang, X., Lu, J., Zhu, D., Wang, J., & Shen, X. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100546 · Cited by 3
Briones, T. L., Woods, J., & Wadowska, M. (2014) · The FASEB Journal · doi:10.1096/fasebj.28.1_supplement.877.1 · Cited by 3
Yang, L., Sheng, J., Qi, S., Yin, Z., Chan, M., Cao, Y., Zhao, H., Wan, Z., Chan, B., Ahn, J. Y., et al. (2026) · Molecular Neurodegeneration · doi:10.1186/s13024-026-00943-3 · Cited by 2
Medina, A., Chen, Y.-C., Zhang, J., Ogden, S. C., Cotsmire, S., Vishwasrao, H. D., Ferrer, M., & Lee, E. M. (2025) · Antiviral Research · doi:10.1016/j.antiviral.2025.106248 · Cited by 2
In Search of Therapeutic Solutions for Alzheimer’s Disease
Ricardo, B., Faras, G., Leonel, E. C. R., & Jos, M. (2012) · InTech eBooks · doi:10.5772/34561 · Cited by 2
Neuroinflammation in Alzheimer's Disease
(2020) · Case Medical Research · doi:10.31525/ct1-nct04274998 · Cited by 2
Membrane-Spanning 4-Domains Subfamily A, MS4A Cluster
Brown, K. S., Turton, J. C., & Morgan, K. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7309-1_8 · Cited by 2
Neuroinflammation in Age-Related Neurodegenerative Diseases
MacPherson, K. P., Rodrigues, M. E. D. S., Cintron, A. F., & Tansey, M. G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811304-2.00016-x · Cited by 2
Glial Reactivity in Response to Neurotoxins: Relevance and Methods
Michalovicz, L. T., & O'Callaghan, J. P. (2019) · Neuromethods · doi:10.1007/978-1-4939-9228-7_4 · Cited by 2
Briones, T. L., Woods, J., & Wadowska, M. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0442-1 · Cited by 2
RetractedImpaired Signaling of NF-κB and NRF2 in CX3CR1-Deficient Microglia: Implications in TauopathiesPreprint
Castro‐Sánchez, S., García‐Yagüe, Á. J., Kügler, S., & Lastres‐Becker, I. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/346304 · Cited by 2
Tran, P. V., Liu, S. X., Harris, A. C., Maxim, Z. L., Munirathinam, M., Muelken, P., Javadova, N., Kruttiventi, S., Kling, P. J., Baack, M. L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.15.648967 · Cited by 2
Zhang, R., Tan, X.-Y., Zhang, Y.-H., Ma, Y.-Z., You, Z.-Y., Huang, Y., & Yang, L.-N. (2025) · Phytotherapy Research · doi:10.1002/ptr.70133 · Cited by 1
G protein-coupled receptors in neurodegenerative diseases
Guimarães, T. R., & Thathiah, A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816228-6.00017-9 · Cited by 1
Sierra, A., Pereira‐Iglesias, M., Martinson, W. D., Falcó, C., Maldonado-Teixidó, J., González-Domínguez, M., Senovilla-Ganzo, R., Benito, E., Beccari, S., Valero, J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.03.685577 · Cited by 1
Anti-bacterial properties of olfactory ensheathing cells and the primary olfactory pathway
Harris, J. (2014) · UTAS Research Repository · doi:10.25959/23225939 · Cited by 1
Microglia demostrate age-dependent performance and interaction with beta-amyloid peptide
Lidónio, G. M. D. C., Brites, D. M. T. O., & Dias, D. M. A. (2013) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Factors from Intact and Damaged Neurons
Mizuno, T. (2013) · Advances in neurobiology · doi:10.1007/978-1-4614-8313-7_3
Leonhardt, J. (2015) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-13510
Mikroglia bei Alzheimer-Demenz
Wiltfang, J. (2014) · Nervenheilkunde · doi:10.1055/s-0038-1627748
N-3 Polyunsaturated Fatty Acid and Neuroinflammation in Aging: Role in Cognition
Layé, S., Madore, C., Delpech, J.-C., Joffre, C., & Nadjar, A. (2014) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-319-06151-1_6
Acosta, S. A. (2011) · Digital Commons - University of South Florida (University of South Florida)
CX3CL1 (chemokine (C-X3-C motif) ligand 1)
Déterre, P. (2014) · Atlas of Genetics and Cytogenetics in Oncology and Haematology · doi:10.4267/2042/53535
Immunoregulatory molecules reveal crosstalk between immune and pain responses
Muramoto, K. (2012) · Folia Pharmacologica Japonica · doi:10.1254/fpj.140.206
Topper, L. A. (2015) · UNM’s Digital Repository (University of New Mexico)
Regulation of LPS-Induced Neuroinflammation by Targeting Microglia in vivo Using Chemogenetics
Binning, W. (2018) · Scholarship@Western (Western University)
Fractalkine signaling in psychiatric disorder : observations in the postmortem brain
Hill, S. L. (2019) · cIRcle (University of British Columbia) · doi:10.14288/1.0384590
Dinesh, A. (2019) · Carleton University's Institutional Repository (MacOdrum Library, Carleton University) · doi:10.22215/etd/2019-13741
Abood, M. T. (2020) · Indian Journal of Forensic Medicine & Toxicology · doi:10.37506/ijfmt.v14i3.10785
Faculty Opinions recommendation of Neuroinflammation in Alzheimer's disease.
Perani, D. (2017) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.725413893.793537457
(2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811351-6.00026-7
Ni, H., Ren, J., Li, X., Wang, J., & Liu, G. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4198951
Sirkis, D. W., Solsberg, C. W., Johnson, T. P., Bonham, L. W., Sturm, V. E., Lee, S. E., Rankin, K. P., Rosen, H. J., Boxer, A. L., Seeley, W. W., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.28.514304
KUŞAT, T., & Emrah, S. U. R. (2023) · doi:10.59287/sbyc.582
Cytokines and Chemokines in the Nervous System in Health and Disease
Azizi, G., & Rostami, A. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95702-1.00248-7
Cytokine status of patients with Alzheimer’s disease
Belousov, V. V., Bogolepova, A. N., Катунина, Е. А., Bulanova, N. V., Mukhin, V. E., & Yudin, S. M. (2025) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro20251250425
Gene Expression in the Hippocampus
Taheri, S., & Abusalim, M. R. S. (2025) · Springer eBooks · doi:10.1007/978-3-031-88907-3_11
Cytokine Status of Patients with Alzheimer’s Disease
Belousov, V. V., Bogolepova, A. N., Катунина, Е. А., Bulanova, N. V., Mukhin, V. E., & Yudin, S. M. (2025) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-025-01876-y
Rommy von Bernhardi, M., Cortes, F., Narea, C., Metz, C., Godoy, G., & Eugenín, J. L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262311378
Furman, S., Zayou, L., Tsourmas, K. I., Javonillo, D. I., Olivarria, G. M., Cheng, Y., Pachow, C., Fernandez, K., Le, L., Edwards, R. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.19.695600
Physical activity and microglial metabolism in neurodegenerative diseases
Andoh, M., & Koyama, R. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27340-7.00013-9
Vautheny, A. (2019) · theses.fr (ABES) · doi:10.70675/1812d71aze8d9z48d6z87d1z5a23a4e81953
Hemonnot-Girard, A.-L. (2021) · theses.fr (ABES) · doi:10.70675/9c8a4775zd774z494ez9bbazf7566faefa8f
Li, R., Fan, J.-Q., & Lin, B. (2026) · Science Advances · doi:10.1126/sciadv.aea6467
Microglial CX3CR1 signaling mediates stress-induced pain behavior in mice
Fülöp, B., Király, Á., Petrák, R., Müller, J., Biró-Sütő, T., Kormos, V., Tékus, V., Rozmer, K., Dénes, Á., Borbély, É., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1869876
de Leeuw, D. M., Duits, F. H., Dicks, E., Vromen, E. M., Teunissen, C. E., Barkhof, F., van der Flier, W. M., Visser, P. J., & Tijms, B. M. (2026) · Brain Communications · doi:10.1093/braincomms/fcag257
Metadata
- Authors
- Cho, S.-H., Sun, B., Zhou, Y., Kauppinen, T. M., Halabisky, B., Wes, P., Ransohoff, R. M., & Gan, L.
- Affiliations
- Gladstone Institutes (US)
- University of California, San Francisco (US)
- Bristol-Myers Squibb (United States) (US)
- Cleveland Clinic (US)
- Corresponding author
- Gan, Li
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 286
- Issue
- 37
- Pages
- 32713-32722
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3173153
- OpenAlex
- W2148721608
- Cited by
- 268
- References
- 52
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 14 · 2023: 20 · 2022: 15 · 2021: 14 · 2020: 16 · 2019: 20 · 2018: 18 · 2017: 17 · 2016: 18 · 2015: 28 · 2014: 27 · 2013: 22 · 2012: 14
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1c06rr018928-01)
- University of California, San Diego
- National Institute on Aging (R01AG030207)
- National Cancer Institute (CO6 RRO18928)
- National Institute of Neurological Disorders and Stroke (P30NS065780)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- CX3CR1, microglial activation, Alzheimer's disease, cognitive impairment, amyloid precursor protein, tau pathology, calbindin, dentate gyrus, neuroinflammation, interleukin-6, TNF-α, memory impairment, novel object recognition, passive avoidance
- MeSH terms
- CX3C Chemokine Receptor 1, Alzheimer Disease, Animals, Cognition Disorders, Disease Models, Animal, Humans, Nerve Tissue Proteins, Signal Transduction, Cytokines, Amyloid beta-Protein Precursor, Microglia, Mice, Knockout, Dentate Gyrus, Receptors, Chemokine, Mice, Calbindins, S100 Calcium Binding Protein G
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
