The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index; 7 of the 29 sources its claims cite were checked for support.
Reduced Angiopoietin-Like 4 Expression in Multiple Sclerosis Lesions Facilitates Lipid Uptake by Phagocytes via Modulation of Lipoprotein-Lipase Activity
Open accessAbstract
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) characterized by the presence of focal demyelinated plaques. Sufficient clearance of myelin and cellular debris is one of the requirements for proper tissue repair and remyelination. The mechanisms underlying the clearance of such debris by phagocytes are not fully understood, but recent findings suggest a prominent role for lipoprotein-lipase (LPL) in this process. Here, we demonstrate that angiopoietin-like 4 (ANGPTL4), a potent inhibitor of LPL, is abundantly expressed in astrocytes in control white matter tissue and its expression is markedly reduced in active MS lesions. We provide evidence that ANGPTL4 inhibits the uptake of myelin-derived lipids by LPL-immunoreactive phagocytes. Taken together, our data suggest that the strong reduction in astrocytic ANGPTL4 expression in active demyelinating MS lesions enables phagocytes to adequately clear myelin debris, setting the stage for remyelination.
Overview
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Written from the paper’s full text.
TL;DR
In active multiple sclerosis lesions, astrocytic ANGPTL4 expression is markedly reduced while LPL is expressed by Iba1-positive phagocytes. ANGPTL4 inhibits LPL activity and myelin-derived lipid uptake by macrophages without blocking myelin phagocytosis, suggesting reduced ANGPTL4 may facilitate debris clearance for repair.
Key findings
- ANGPTL4 was predominantly expressed by GFAP-positive astrocytes in control/NAWM tissue and was consistently reduced in active MS lesions compared with surrounding NAWM and inactive lesions (one-way ANOVA; N = 6 NAWM, 5 active, 4 inactive; *p < 0.05).
- LPL was weakly expressed in NAWM but abundantly expressed in active lesions, localized to Iba1-positive macrophages/microglia.
- Myelin exposure did not affect astrocytic ANGPTL4 expression (Mann–Whitney; N = 8 control, 11 myelin), but coculture with alternatively activated macrophages significantly reduced astrocytic ANGPTL4 (Student’s t-test; N = 7; p < 0.01).
- ANGPTL4 inhibited macrophage LPL activity (Mann–Whitney; N = 4) and reduced Oil-Red-O lipid accumulation after myelin exposure, similar to Orlistat (one-way ANOVA; N = 5), but did not inhibit phagocytosis of Atto633-labeled myelin; Cytochalasin D completely blocked phagocytosis (one-way ANOVA; N = 5; *p < 0.05, p < 0.01, p ≤ 0.0001).
Methods
- Immunohistochemistry and immunofluorescence were performed on formalin-fixed paraffin-embedded post-mortem brain tissue from 12 MS patients and 3 non-neurological controls, with active, inactive, and NAWM regions classified by PLP and HLA-DR staining.
- Human astrocytoma U373 cells and human monocyte-derived macrophages were used in culture; macrophages were differentiated with M-CSF and alternatively activated with IL-4, and astrocyte/macrophage coculture used transwell inserts.
- Myelin was isolated from three healthy control CNS white matter samples and labeled with Atto633; outcomes included qPCR, Oil-Red-O staining, FACS-based myelin phagocytosis, and a fluorometric LPL activity assay, analyzed with t-tests, Mann–Whitney U-tests, or one-way ANOVA in GraphPad Prism 5.0.
Limitations
- The paper does not include a dedicated limitations section; the discussion states that future studies are needed to understand how macrophages regulate astrocytic ANGPTL4 production.
- The discussion also notes that global ANGPTL4 knockout mice did not show significant differences in brain LPL activity, which may relate to lack of LPL protein expression in control white matter.
- Evident from the text: sample sizes are small (e.g., N = 4–11 per experiment; 12 MS and 3 control brains), astrocyte experiments use U373 astrocytoma cells rather than primary human astrocytes, and the study is largely in vitro/human tissue correlative without direct in vivo remyelination or functional repair data.
Model-written summary. Check it against the paper before relying on it.
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Verification
Claims the paper makes
7 of 29 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured
- Premisecitation
LPL plays an important role during initiation of remyelination.
“evidence is emerging that lipoprotein-lipase (LPL), an enzyme involved in lipid-processing, plays an important role during initiation of remyelination (4, 6).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [4] Olah, 2012, Identification of a microglia phenotype supportive of remyelination, Glia. source
The gene-expression section reports that Lpl, a lipid-recycling factor, was strongly expressed in lesion-associated microglia before remyelination and remained expressed during remyelination. The Discussion suggests a supportive role for microglial lipid processing, but does not establish that LPL itself plays an important role specifically in initiating remyelination. Page numbers were not available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [6] Bruce, 2018, Lipoprotein lipase is a feature of alternatively-activated microglia and may facilitate lipid uptake in the CNS during demyelination, Front Mol Neurosci. source
- Premisecitation
LPL protein expression is lacking in control white matter brain tissue.
“the lack of LPL protein expression in control white matter brain tissue (17).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [17] Wang, 2012, Lipoprotein lipase in the brain and nervous system, Annu Rev Nutr. source
The section “LPL mRNA, Protein, and Enzyme Activity in Brain and CNS” (page unavailable) reports very low LPL protein levels in glial-rich areas adjacent to neurons. It does not establish that LPL protein is absent from control brain white matter specifically; it also reports LPL protein on brain vascular endothelium. (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Findingown data
ANGPTL4 does not inhibit phagocytosis of myelin by macrophages.
“Phagocytosis of atto633-labeled myelin was not inhibited by ANGPTL4”
- Also stated in: § Discussion · plain
“we did not observe differences in their capacity to phagocytose myelin”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Myelin treatment increases lipid accumulation in macrophages.
“we observed increased lipid accumulation after myelin treatment”
- Also stated in: § Discussion · boosted
“Upon exposure to myelin fragments, the lipid storage in macrophages was dramatically increased as determined by Oil-Red-O staining.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · boosted
- Findingown data
ANGPTL4 significantly decreases LPL activity in macrophages.
“we confirmed that ANGPTL4 causes a significant decrease in LPL activity in macrophages compared to non ANGPTL4 treated macrophages”
Quote in the paperSubstantial claim
- Findingown data
Exposure to myelin does not affect ANGPTL4 expression in human astrocytes.
“Exposure to myelin did not affect ANGPTL4 expression in astrocytes”
Quote in the paperSubstantial claim - Findingown data
ANGPTL4 expression in inactive MS lesions is similar to that in normal appearing white matter.
“while in inactive lesions the expression of ANGPTL4 displayed similar immunoreactivity as observed in NAWM”
Quote in the paperNot a substantial claim - Findingown data
ANGPTL4 expression is markedly reduced in active MS lesions compared to normal appearing white matter.
“its expression is markedly reduced in active MS lesions”
- Also stated in: § Decreased Astrocytic ANGPTL4 Expression in Multiple Sclerosis Lesions · plain
“we observed a marked decreased expression of ANGPTL4 in active MS lesions compared to NAWM”
- Also stated in: § Decreased Astrocytic ANGPTL4 Expression in Multiple Sclerosis Lesions · boosted
“ANGPTL4 immunoreactivity is consistently reduced in active MS lesions compared to surrounding NAWM and to inactive lesions”
Quote in the paperSubstantial claim - Also stated in: § Decreased Astrocytic ANGPTL4 Expression in Multiple Sclerosis Lesions · plain
- Findingown data
ANGPTL4 is abundantly expressed by astrocytes in control white matter tissue.
“is abundantly expressed in astrocytes in control white matter tissue”
- Also stated in: § Decreased Astrocytic ANGPTL4 Expression in Multiple Sclerosis Lesions · plain
“ANGPTL4 was found to be expressed in normal appearing white matter by cells with an astrocytic morphology.”
Quote in the paperSubstantial claim - Also stated in: § Decreased Astrocytic ANGPTL4 Expression in Multiple Sclerosis Lesions · plain
- Findingown data
LPL in active MS lesions is localized to Iba1-positive macrophages/microglia.
“Immunofluorescent double staining with Allograft inflammatory factor 1 (iba1, macrophage/microglia marker) confirmed the cellular localization of LPL in macrophages/microglia”
Quote in the paperSubstantial claim - Findingown data
Cytochalasin D completely prevents myelin phagocytosis by macrophages.
“treatment with Cytochalasin D, which blocks phagocytosis, completely prevented the myelin phagocytosis by macrophages”
Quote in the paperSubstantial claim - Findingown data
ANGPTL4 is predominantly expressed by GFAP-positive astrocytes.
“co-localization studies which confirmed that ANGPTL4 is predominantly expressed by glial fibrillary acidic protein (GFAP)-positive astrocytes”
Quote in the paperNot a substantial claim - Findingown data
Coculture with activated macrophages significantly decreases ANGPTL4 expression in human astrocytes.
“Astrocytes cultured in the presence of activated macrophages showed a significant decreased expression of ANGPTL4 compared to astrocytes cultured in the absence of macrophages”
- Also stated in: § Discussion · plain
“Astrocytes cultured in the presence of alternatively stimulated macrophages showed a significant reduction in the expression in astrocytic ANGPTL4.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
ANGPTL4 treatment decreases lipid uptake/accumulation in myelin-exposed macrophages.
“Macrophages that were treated with ANGPTL4 peptide during exposure to myelin displayed decreased Oil-Red-O staining, demonstrating that ANGPTL4 inhibits (myelin) lipid uptake.”
Quote in the paperSubstantial claim - Findingown data
Orlistat treatment reduces Oil-Red-O staining in myelin-exposed macrophages similarly to ANGPTL4.
“Treatment with Orlistat resulted in similar reduction as ANGPTL4.”
Quote in the paperSubstantial claim - Premisecitation
Full global knockout of ANGPTL4 in mice does not show significant differences in LPL activity in the brain.
“full global knockout of ANGPTL4 in mice did not show any significant differences in LPL activity in the brain (16).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] Vienberg, 2015, Differential effects of angiopoietin-like 4 in brain and muscle on regulation of lipoprotein lipase activity, Mol Metab. source
- Premisecitation
LPL is involved in lipid and lipoprotein uptake in microglia.
“shows to be involved in lipid and lipoprotein uptake in microglia (6).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Bruce, 2018, Lipoprotein lipase is a feature of alternatively-activated microglia and may facilitate lipid uptake in the CNS during demyelination, Front Mol Neurosci. source
- Premisecitation
ANGPTL4 is a potent inhibitor of LPL.
“our group described the presence of, angiopoietin-like 4 (ANGPTL4), a potent inhibitor of LPL, in astrocytes (8).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Chakraborty, 2018, Angiopoietin like-4 as a novel vascular mediator in capillary cerebral amyloid angiopathy, Brain. source
- Interpretationown data
Reduced astrocytic ANGPTL4 expression in active demyelinating MS lesions enables phagocytes to adequately clear myelin debris, setting the stage for remyelination.
“our data suggest that the strong reduction in astrocytic ANGPTL4 expression in active demyelinating MS lesions enables phagocytes to adequately clear myelin debris, setting the stage for remyelination.”
- Also stated in: § Discussion · hedged
“This finding suggests that loss of astrocytic ANGPTL4 expression in active demyelinating MS lesions might be a protective mechanism enabling phagocytes to effectively remove myelin debris paving the way for repair.”
Quote in the paperSubstantial claim- Rests on an assumption: LPL hydrolyses triglycerides into glycerol and free fatty acids.
- Also stated in: § Discussion · hedged
- Interpretationreasoning
Macrophages utilize LPL in the process of myelin clearance.
“Our findings suggest that macrophages utilize LPL in the process of myelin clearance.”
Quote in the paperSubstantial claim- Rests on an assumption: LPL hydrolyses triglycerides into glycerol and free fatty acids.
- Interpretationown data
Astrocyte-derived ANGPTL4 inhibits LPL activity, leading to decreased myelin-derived lipid uptake by macrophages by mechanisms other than phagocytosis.
“these findings show that astrocyte derived ANGPTL4 inhibits LPL activity, leading to decreased myelin derived lipid uptake by macrophages by mechanisms other than phagocytosis.”
Quote in the paperSubstantial claim- Rests on an assumption: LPL hydrolyses triglycerides into glycerol and free fatty acids.
- Premisecitation
LPL activity is significantly increased in brain tissue of the EAE model at the point when clinical symptoms start to decrease.
“Activity of this enzyme is significantly increased in brain tissue of the EAE model at the point when clinical symptoms start to decrease”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Bruce, 2018, Lipoprotein lipase is a feature of alternatively-activated microglia and may facilitate lipid uptake in the CNS during demyelination, Front Mol Neurosci. source
- Premisecitation
Resulting free fatty acids can be taken up via scavenger receptors such as CD36 and CD68 by microglia.
“The resulting FFAs can in turn be taken up via scavenger receptors, such as CD36 and CD68 by microglia (22).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] Goldberg, 2009, Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways, J Lipid Res. source
- Interpretationown data
ANGPTL4 inhibits uptake of myelin-derived lipids by LPL-immunoreactive phagocytes.
“We provide evidence that ANGPTL4 inhibits the uptake of myelin-derived lipids by LPL-immunoreactive phagocytes.”
- Also stated in: § Discussion · boosted
“We provide evidence that ANGPTL4 inhibits uptake of myelin-derived lipids by LPL-immunoreactive phagocytes.”
Quote in the paperSubstantial claim- Rests on an assumption: LPL hydrolyses triglycerides into glycerol and free fatty acids.
- Also stated in: § Discussion · boosted
- Interpretationcitation
LPL-expressing phagocytes might contribute to repair and support remyelination through clearance and reuptake of lipid debris.
“This suggests that LPL-expressing phagocytes might contribute to repair and support remyelination through the clearance and reuptake of lipid debris.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Bruce, 2018, Lipoprotein lipase is a feature of alternatively-activated microglia and may facilitate lipid uptake in the CNS during demyelination, Front Mol Neurosci. source
- Premisecitation
Removal of damaged myelin components and apoptotic cells is requisite for remyelination.
“Removal of damaged myelin components and apoptotic cells is a requisite for remyelination (4, 5).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Lipid-laden microglia/macrophages are immunosuppressive.
“lipid-laden microglia/macrophages are immunosuppressive (20)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [20] Boven, 2006, Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis, Brain. source
- It may state two separate claims as one. 6
- Probably not a substantial claim. 10
It may state two separate claims as one.
PremisecitationLPL mRNA expression is almost exclusively detected in microglia/macrophage and specifically in alternatively activated microglia/macrophages.
“LPL mRNA expression was almost exclusively detected in microglia/macrophage and specifically in alternatively activated microglia/macrophages (18, 19).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [18] Zhang, 2014, An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex, J Neurosci. source
The cell-type expression and microglia-purification sections discuss microglia, but the passages found do not report LPL mRNA expression. Searches for Lpl/lipoprotein lipase and alternatively activated microglia/macrophages found no passage addressing either part of the claim. (LLM, conf=0.72)
Experimental — accuracy not yet measured - cites [19] Zhang, 2016, Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse, Neuron. source
The Results sections on cell-type transcriptomes and reactive astrocytes discuss microglia or macrophage responses, but do not address LPL mRNA or alternatively activated microglia/macrophages. Searches for “LPL” and “lipoprotein lipase” found no passage supporting the claimed expression pattern. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Probably not a substantial claim.
PremisecitationRecent reports highlight a pivotal role of microglial LPL in remyelination.
“Recent reports have highlighted the pivotal role of microglial LPL in remyelination (4, 6, 12)”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [4] Olah, 2012, Identification of a microglia phenotype supportive of remyelination, Glia. source
The gene-expression confirmation section reports strong Lpl mRNA expression in lesion-associated microglia during demyelination and remyelination. The Discussion interprets this as an indication that microglia may support remyelination through lipid recycling, but it does not establish that LPL itself has a pivotal functional role. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [6] Bruce, 2018, Lipoprotein lipase is a feature of alternatively-activated microglia and may facilitate lipid uptake in the CNS during demyelination, Front Mol Neurosci. source
- cites [12] Huey, 2002, Lipoprotein lipase is expressed in rat sciatic nerve and regulated in response to crush injury, J Lipid Res. source
It may state two separate claims as one.
Findingown dataLPL is weakly expressed in normal appearing white matter and abundantly expressed in active MS lesions.
“LPL was weakly expressed in NAWM and abundantly expressed in active lesions”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationMacrophage depletion in an experimental MS animal model significantly reduces clinical symptoms.
“Macrophage depletion in an experimental MS animal model significantly reduces clinical symptoms underscoring the pathogenic role of these cells (1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Huitinga, 1990, Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages, J Exp Med. source
It may state two separate claims as one.
PremisecitationPhagocytes promote clearance of cellular debris after myelin damage, which is a prerequisite for remyelination.
“phagocytes promote the clearance of cellular debris after myelin damage, which is a prerequisite for remyelination (14, 15).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [14] Kotter, 2005, Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression, Neurobiol Dis. source
- cites [15] Merson, 2010, Role of cytokines as mediators and regulators of microglial activity in inflammatory demyelination of the CNS, Neuromolecular Med. source
It may state two separate claims as one.
Interpretationown dataCrosstalk between macrophages and astrocytes is involved in and necessary for downregulation of astrocytic ANGPTL4 expression.
“We show that the cellular communication between astrocytes and macrophages is necessary for the downregulation of astrocytic ANGPTL4 expression.”
- Also stated in: § Discussion · hedged
“It thus appears that crosstalk between alternatively activated macrophages and astrocytes is involved in the downregulation of astrocytic ANGPTL4.”
Quote in the paperSubstantial claim- Also stated in: § Discussion · hedged
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenGFAP and ANGPTL4 fluorescence intensity were measured by a blinded observer.
“GFAP and ANGPTL4 fluorescence intensity were measured by a blinded observer using ImageJ software”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationRegulation of phagocyte function and activity is under control of astrocytes.
“Regulation of phagocyte function and activity is under control of astrocytes (7)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] Smith, 2000, Astrocytes modulate macrophage phagocytosis of myelin in vitro, J Neuroimmunol. source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationMyelin debris induces a reactive astrocyte profile.
“myelin debris, which has been shown to induce a reactive astrocyte profile (21)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Ponath, 2017, Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology, Brain. source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationScavenger receptors are suggested to be involved in myelin phagocytosis and are upregulated in and around demyelinating areas in MS tissue.
“These scavenger receptors have been suggested to involved in myelin phagocytosis and have been shown to be upregulated in and around demyelinating areas in MS tissue (13).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Hendrickx, 2013, Selective upregulation of scavenger receptors in and around demyelinating areas in multiple sclerosis, J Neuropathol Exp Neurol. source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationANGPTL4 is expressed by astrocytes in white matter and gray matter of patients with capillary cerebral amyloid angiopathy.
“We previously demonstrated that angiopoietin-like 4 (ANGPTL4) is expressed by astrocytes in white matter and in gray matter of patients suffering from capillary cerebral amyloid angiopathy (8).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] Chakraborty, 2018, Angiopoietin like-4 as a novel vascular mediator in capillary cerebral amyloid angiopathy, Brain. source
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationMicroglial LPL processes myelin, after which myelin-derived lipids can be taken up via scavenger receptors on microglia.
“it is thought that microglial LPL is able to process myelin after which the myelin derived lipids can be taken up via scavenger receptors expressed on microglia (13).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Hendrickx, 2013, Selective upregulation of scavenger receptors in and around demyelinating areas in multiple sclerosis, J Neuropathol Exp Neurol. source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationIntravenous administration of anti-inflammatory macrophages or microglia reduces clinical signs in experimental autoimmune encephalomyelitis.
“intravenous administration of anti-inflammatory macrophages or microglia reduced clinical signs in the MS animal model experimental autoimmune encephalomyelitis (EAE) (2, 3).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [2] Zhang, 2014, Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice, Glia. source
- cites [3] Mikita, 2011, Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration, Mult Scler J. source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationANGPTL4-mediated inhibition of LPL limits formation of foam cells in atherosclerosis.
“ANGPTL4 mediated inhibition of LPL has been shown to limit the formation of foam cells in the context of atherosclerosis (23, 24).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [23] Aryal, 2016, ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression, Nat Commun. source
- cites [24] Georgiadi, 2013, Overexpression of angiopoietin-like protein 4 protects against atherosclerosis development, Arterioscler Thromb Vasc Biol. source
The paper relies on this without support.
LPL hydrolyses triglycerides into glycerol and free fatty acids.
“LPL hydrolyses triglycerides into glycerol and free fatty acids (FFA).”
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Metadata
- Authors
- Kamermans, A., Rijnsburger, M., Chakraborty, A., van der Pol, S., de Vries, H. E., & van Horssen, J.
- Affiliations
- Amsterdam Neuroscience (NL)
- Corresponding author
- van Horssen, Jack
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2019-05-03
- Volume
- 10
- Pages
- 950-950
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC6509157
- OpenAlex
- W2943302790
- Cited by
- 25
- References
- 26
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 1
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Stichting MS Research (MS-14-358e, AK)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- ANGPTL4, lipoprotein lipase, multiple sclerosis, demyelination, myelin debris clearance, phagocytes, astrocytes, remyelination, lipid uptake, demyelinating lesions, white matter
- MeSH terms
- Angiopoietin-Like Protein 4, Adult, Aged, Aged, 80 and over, Brain, Female, Humans, Lipoprotein Lipase, Macrophages, Male, Middle Aged, Multiple Sclerosis, Myelin Sheath, Phagocytes, Cell Line, Tumor, Lipid Metabolism
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.
A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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 ›
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