The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Amyloid-β-Induced Astrocytic Phagocytosis is Mediated by CD36, CD47 and RAGE
Abstract
Astrocytes, the most numerous glial cell in the brain, have multiple functions and are key to maintenance of homeostasis in the central nervous system. Microglia are the resident immunocompetent cells in the brain and share several functions with macrophages, including their phagocytic ability. Indeed microglia are the resident phagocytes in the brain and express numerous cell surface proteins which act to enable receptor-mediated phagocytosis. However recent evidence suggests that astrocytes express some genes which permit phagocytosis of phosphatidylserine-decorated cells and this probably explains sporadic reports in the literature which suggest that astrocytes become phagocytic following brain trauma. Here we examined the potential of astrocytes to phagocytose fluorescently-labelled latex beads and amyloid-β (Aβ) and report that they competently engulf both in a manner that relies on actin polymerization since it was inhibited by cytochalasin D. The data indicate that incubation of cultured astrocytes or microglia with Aβ increased phagocytosis and markers of activation of both cell types. Aβ was found to markedly increase expression of the putative Aβ-binding receptors CD36 and CD47 in astrocytes, while it decreased expression of the receptor for advanced glycation endproducts (RAGE). It is demonstrated that blocking these receptors using a neutralizing antibody attenuated Aβ-induced phagocytosis of latex beads by astrocytes. Interestingly blocking these receptors also decreased uptake of beads even in the absence of Aβ. Here we demonstrate that astrocytes are competent phagocytes and are capable of engulfing Aβ.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Blocking receptors including CD36, CD47, and RAGE with neutralizing antibodies can attenuate astrocytic phagocytosis of Aβ, implicating they are putative Aβ receptors in astrocytes [407].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [407]
Citations
Cites
Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129
Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
Hickman, S. E., Allison, E. K., & El Khoury, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0616-08.2008 · Cited by 1,329
Simard, A. R., Soulet, D., Gowing, G., Julien, J.-P., & Rivest, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.022 · Cited by 1,265
El Khoury, J., Toft, M., Hickman, S. E., Means, T. K., Terada, K., Geula, C., & Luster, A. D. (2007) · Nature Medicine · doi:10.1038/nm1555 · Cited by 915
Adult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909
Streit, W. J., Braak, H., Xue, Q.-S., & Bechmann, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0556-6 · Cited by 727
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701
Functions and molecular mechanisms of the CD47–SIRPα signalling pathway
Matozaki, T., Murata, Y., Okazawa, H., & Ohnishi, H. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.12.001 · Cited by 481
Koenigsknecht-Talboo, J., & Landreth, G. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1808-05.2005 · Cited by 477
Microglial Phagocytosis of Fibrillar β-Amyloid through a β1Integrin-Dependent Mechanism
Koenigsknecht-Talboo, J., & Landreth, G. E. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2557-04.2004 · Cited by 455
Cited by
Sorted by citations
Items 101–148 of 148
Immune modulations and immunotherapies for Alzheimer’s disease: a comprehensive review
Mahdiabadi, S., Momtazmanesh, S., Perry, G. L., & Rezaei, N. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2021-0092 · Cited by 13
Saaoud, F., Liu, L., Xu, K., Lu, Y., Shao, Y., Issa, M., Jiang, X., Wang, X., Liu, X., Autieri, M. V., et al. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251329583 · Cited by 13
“23 After the proteolytic production of A β by γ -secretase, A β peptides have the capability to activate glial cells through a range of PRRs, including CD14, CD36, RAGE, TREM2, and TLRs. 28 The innate immune system can also regulate γ -secretase activity through cytokine signaling, such as via interferon-induced trans…”
Transglutaminases Derived from Astrocytes Accelerate Amyloid β Aggregation
Kawabe, K., Takano, K., Moriyama, M., & Nakamura, Y. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2258-0 · Cited by 10
“Several candidate molecules for Aβ uptake by astrocytes are reported; lipoprotein receptor related protein (LRP), receptor of advanced glycation end product (RAGE), CD36 and CD47 [35]; however, detail is unclear.”
Zhao, Z., Hood, R. J., Ong, L. K., Pietrogrande, G., Sanchez‐Bezanilla, S., Warren, K. E., Ilicic, M., Kluge, M. G., TeBay, C., Ottersen, O. P., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.585189 · Cited by 7
“The increase in RAGE may be best interpreted by considering the role of RAGE in facilitating microglial chemotaxis toward Aβ (59) and/or phagocytosis (60, 61).”
BackgroundThe Implication of Glial Metabotropic Glutamate Receptors in Alzheimer’s Disease
de Lima, I. B. Q., & Ribeiro, F. M. (2021) · Current Neuropharmacology · doi:10.2174/1570159x20666211223140303 · Cited by 9
“It was previously demonstrated that CD36 is one of the mediators of the phagocytosis induced by Aβ in these cells [262].”
Mechanisms of increased Alzheimer’s disease pathology with R47H and R62H TREM2 variants
Fancy, N. N., Willumsen, N., Chau, V. M. N., Boulger, S. L., Whitwell, H. J., Wang, W., Avot, B., Thomas, M., Talbot-Martin, J., Tsartsalis, S., et al. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03036-z · Cited by 8
Beclin 1 regulates astrocyte phagocytosis and phagosomal recruitment of retromer
Silva, E. G. L., Delgadillo, Y., White, R., & Lucin, K. M. (2023) · Tissue and Cell · doi:10.1016/j.tice.2023.102100 · Cited by 6
Metformin treatment confers protection of the optic nerve following photoreceptor degeneration
Eltony, S. A., Mohaseb, H. S., Sayed, M. M., & Ahmed, A. (2021) · Anatomy & Cell Biology · doi:10.5115/acb.20.320 · Cited by 6
“It has been reported that astrocytes participate in phagocytosis of cerebral white matter myelin in adult rabbit [38], in Wallerian degeneration of the opossum’s optic nerve [39] and following brain trauma [40].”
BackgroundZhou, W., Yin, X., Huang, J., Fu, L., Yadav, H., Yao, W., Chu, D., & Wu, F. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117233 · Cited by 5
The identification of a Distinct Astrocyte Subtype that Diminishes in Alzheimer’s Disease
Wei, H., Withrow, J. S., Rakshit, J., Amin, F. U., Nahm, J., Mowry, F. E., Mao, Z., Bhattacharjee, M. B., Zhu, J., Yang, Y., et al. (2024) · Aging and Disease · doi:10.14336/ad.2024.0205-1 · Cited by 7
“Moreover, prior studies have demonstrated the ability of astrocytes to phagocytose Aβ [73].”
Paul, D., & Basavan, D. (2022) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-022-00446-0 · Cited by 5
Role of astrocytes in Alzheimer's disease pathogenesis and the impact of exercise-induced remodeling
Shao, J., Deng, Q., Feng, S., Wu, C., Liu, X., & Yang, L. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150418 · Cited by 5
γ-Secretase fanning the fire of innate immunity
Liu, C., Nikain, C., & Li, Y.-M. (2023) · Biochemical Society Transactions · doi:10.1042/bst20221445 · Cited by 4
BMAL1-GPX3 axis in the choroid plexus mitigates Aβ pathology in an amyloid mouse model
Tang, F., Li, Y., Bai, X., Zhu, Z., Dong, H., Chen, J., Ye, B., Yuan, M., Wu, Q., Fu, W., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03691-9 · Cited by 6
“On one hand, they are capable of encapsulating and partially phagocytosing Aβ [59].”
Huang, N., Hong, R., Cui, X., Cao, L., Shi, L., Chen, B., Su, Y., Xu, X., Hua, C., & Ying, T. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04297-2 · Cited by 5
“Proinflammatory factors are known to suppress the expression of binding receptors on microglia and attenuate their phagocytic function [73, 74].”
CD36 gene polymorphisms and Alzheimer's disease
Šerý, O., Goswami, N., & Balcar, V. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-815868-5.00004-9 · Cited by 4
Neuroimmune Dynamics in Alzheimer’s Disease Progression
Andrade, V., Guzmán‐Martínez, L., Vergara-Pulgar, K., & Maccioni, R. B. (2017) · InTech eBooks · doi:10.5772/intechopen.68941 · Cited by 4
Structure and function analyses of the SRC gene in Pacific white shrimp Litopenaeus vannamei
Si, S., Zhang, X., Yu, Y., Zhong, X., Zhang, X., Yuan, J., & Li, F. (2024) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2024.109433 · Cited by 3
Pezeshki, S. P., Darabi, M. K., Nazeri, Z., Sarkaki, A., Rashidi, M., Babaahmadi‐Rezaei, H., Kheirollah, A., & Cheraghzadeh, M. (2023) · PubMed Central · doi:10.22088/ijmcm.bums.12.2.108 · Cited by 3
In Vitro Engulfment Assay to Measure Phagocytic Activity of Astrocytes Using Synaptosomes
Byun, Y. G., & Chung, W. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9068-9_11 · Cited by 3
Lysosomal Acidification in Cultured Astrocytes Using Nanoparticles
Lööv, C., & Erlandsson, A. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6934-0_10 · Cited by 4
The Maillard reaction and food allergy: Impacts on sensitisation and on elicitation
Teodorowicz, G., Bastiaan‐Net, S., Hoppenbrouwers, T., & Wichers, H. J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-96018-2.00142-5 · Cited by 3
Nanomaterial‐based immune therapeutic strategies in neurodegenerative diseases
Zhou, X., Liu, J., Lai, S., Yin, S., Luo, B., Shao, L., & Kang, Y. (2025) · BMEMat · doi:10.1002/bmm2.70050 · Cited by 2
The Role of Astrocytes in Astrocytes Alzheimer’s Disease
Mavroudis, I. A., Petridis, F., Chatzikonstantinou, S., McKENN, J., Karantali, E., & KAZIS, D. (2020) · Annals of the Academy of Romanian Scientists Series on Biological Sciences · doi:10.56082/annalsarscibio.2020.1.65 · Cited by 2
Inflammation in Alzheimer's Disease: Cross-talk between Lipids and Innate Immune Cells of the Brain
Ai, L., & Me, C. (2015) · Cited by 2
CD11c is not required by microglia to convey neuroprotection after prion infection
Carroll, J. A., Striebel, J. F., Baune, C., Chesebro, B. W., & Race, B. (2023) · PLoS ONE · doi:10.1371/journal.pone.0293301 · Cited by 2
Gupta, A., Thirugnanam, K., Bice, Z., Lowman, A. K., Rarick, K. R., LaViolette, P. S., Pan, A., Franczak, M. B., & Ramchandran, R. (2026) · BMC Molecular and Cell Biology · doi:10.1186/s12860-026-00581-z · Cited by 1
Inflammation and the Pathophysiology of Astrocytes in Neurodegenerative Diseases
Meares, G. P., & Benveniste, E. N. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1071-7_4 · Cited by 1
Role of Reactive Astrocytes in Alzheimer’s Disease
Sarkar, S., Guha, S., & Biswas, S. C. (2022) · Springer eBooks · doi:10.1007/978-981-16-8313-8_9 · Cited by 1
Fatima, A., & Daou, A. (2024) · Journal of Student Research · doi:10.47611/jsrhs.v13i1.6191 · Cited by 1
“Cultured astrocytes engulf Aß in a process conditional to the Aß binding receptors CD36 and CD47 (Jones et al., 2012) and at times are reliant on APOE that is localized to plaques-associated reactive astrocyte mechanism for the degradation of Aß (Jiang et al., 2008).”
BackgroundHopley, R. T., Haller, E. M., Rojiani, M. V., & Rojiani, A. M. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx084 · Cited by 1
Cellular and Molecular Responses to Traumatic Brain Injury
Lööv, C. (2014) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Regenerating the brain: Stem cell differentiation and cholinergic dysfunction in Alzheimer disease
Malmsten, L. (2014) · Figshare
Resolution of inflammation in Alzheimer’s disease
Wang, X. (2014) · Figshare
Using TUDCA to treat Alzheimer's disease after pathology onset in APP/PS1 mice
Dionísio, P. (2014) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Using TUDCA to treat Alzheimer's disease after pathology onset in APP/PS1 mice
Farmácia, F. D. (2014)
Lynch, M. A., & Minogue, A. M. (2014) · Arrow@dit (Dublin Institute of Technology)
Self-citationThe Neuroimmune Biology of Phagocytosis
Quintanar‐Stephano, A., Viñuela‐Berni, V., Kovács, K., & Berczi, I. (2017) · Advances in Neuroimmune Biology · doi:10.3233/nib-150104
Xu, Y., Gao, Y., Qian, L., Feng, W., Song, T., Li, Y., Guo, F., Zheng, J., Li, Y., Zhang, J., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-946298/v1
CD44 Might Promote the Migration and Invasion of Ovarian Cancer by Regulating CD36Preprint
Gao, Y., Shi, R., Dong, J., Feng, W., Dang, Y., Song, T., Li, Y., Guo, F., Jiao, Z., Yu, L., et al. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4645301
Verapamil Alleviates Astrocytic Glycolytic Dysfunction Via Txnip Inhibition in 3×Tg-Ad MicePreprint
Zhou, W., Yin, X., Huang, J., Fu, L., Yadav, H., Yao, W., Chu, D., & Wu, F. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5235929
Dai, D. L., Li, M., & Lee, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26608141
Dai, D. L., Li, M., & Lee, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26608144
Hopx expression marks Aβ clearance astrocytes in Alzheimer’s diseasePreprint
Cao, D.-D., Dong, J., Liao, X.-Y., Teng, Y.-Y., Gu, Y., & Luo, Z. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.27.708674
Wang, T., Wang, L., Cao, J., Zhao, Y., He, Z., & Lu, F. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1956600
“MEGF10-and MERTK-dependent astrocytic engulfment supports adult hippocampal circuit homeostasis; in AD, it may remove dystrophic synapses but may also become inef fi cient because of A b -associated dysfunction (101 – 103).”
Metadata
- Authors
- Jones, R. S., Minogue, A. M., Connor, T. J., & Lynch, M. A.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Minogue, Aedín M.
- ORCID
- Lynch, Marina A.
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2012-12-14
- Volume
- 8
- Issue
- 1
- Pages
- 301-311
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- OpenAlex
- W2036955747
- Cited by
- 147
- References
- 46
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 10 · 2023: 9 · 2022: 13 · 2021: 19 · 2020: 17 · 2019: 6 · 2018: 7 · 2017: 15 · 2016: 12 · 2015: 7 · 2014: 15 · 2013: 2
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Board
- Science Foundation Ireland
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- amyloid-beta, astrocytes, phagocytosis, CD36, CD47, RAGE, actin polymerization, microglia, receptor-mediated phagocytosis, receptor antagonists, neuroinflammation
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Animals, Newborn, Astrocytes, Cell Survival, Flow Cytometry, Fluorescent Dyes, Glial Fibrillary Acidic Protein, L-Lactate Dehydrogenase, Microspheres, Phagocytosis, Receptors, Immunologic, RNA, Messenger, Amyloid beta-Peptides, Fluorescein-5-isothiocyanate, Rats, Wistar, Microglia, CD36 Antigens, Excitatory Amino Acid Transporter 2, CD11b Antigen, Rats, CD47 Antigen
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
