The DOI matches its Crossref record; 68 of the 69 references it cites were found in a registry or an index; 34 of the 74 sources its claims cite were checked for support.
Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice
Open accessAbstract
The accumulation of aggregated amyloid‐β (Aβ) in amyloid plaques is a neuropathological hallmark of Alzheimer's disease (AD). Reactive astrocytes are intimately associated with amyloid plaques; however, their role in AD pathogenesis is unclear. We deleted the genes encoding two intermediate filament proteins required for astrocyte activation—glial fibrillary acid protein ( Gfap ) and vimentin ( Vim )—in transgenic mice expressing mutant human amyloid precursor protein and presenilin‐1 (APP/PS1). The gene deletions increased amyloid plaque load: APP/PS1 Gfap –/– Vim –/– mice had twice the plaque load of APP/PS1 Gfap +/+ Vim +/+ mice at 8 and 12 mo of age. APP expression and soluble and interstitial fluid Aβ levels were unchanged, suggesting that the deletions had no effect on APP processing or Aβ generation. Astrocyte morphology was markedly altered by the deletions: wild‐type astrocytes had hypertrophied processes that surrounded and infiltrated plaques, whereas Gfap –/– Vim –/– astrocytes had little process hypertrophy and lacked contact with adjacent plaques. Moreover, Gfap and Vim gene deletion resulted in a marked increase in dystrophic neurites (2‐ to 3‐fold higher than APP/PS1 Gfap +/+ Vim +/+ mice), even after normalization for amyloid load. These results suggest that astrocyte activation limits plaque growth and attenuates plaque‐related dystrophic neurites. These activities may require intimate contact between astrocyte and plaque.—Kraft, A. W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S. C., Brown, J., Wilhelmsson, U., Restivo, J. L., Cirrito, J. R., Holtzman, D. M., Kim, J., Pekny, M., Lee, J.‐M. Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice. FASEB J. 27, 187–198 (2013). www.fasebj.org
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Deleting astrocyte intermediate filament genes *Gfap* and *Vim* in APP/PS1 mice increased amyloid plaque load and dystrophic neurites without changing APP processing or soluble/interstitial Aβ levels. The results suggest that activated astrocytes limit plaque growth and plaque-related neuritic dystrophy, likely requiring intimate astrocyte–plaque contact.
Key findings
- APP/PS1 *Gfap*−/−*Vim*−/− mice had twice the plaque load of APP/PS1 *Gfap*+/+*Vim*+/+ mice at 8 and 12 mo of age, with no difference at 4 mo.
- APP expression, soluble Aβ, interstitial fluid Aβ levels, and ISF Aβ half-life were unchanged, suggesting no effect on APP processing or Aβ generation.
- Dystrophic neurites were 2- to 3-fold higher in APP/PS1 *Gfap*−/−*Vim*−/− mice than in APP/PS1 *Gfap*+/+*Vim*+/+ mice, even after normalization for amyloid load.
- Wild-type astrocytes had hypertrophied processes that surrounded and infiltrated plaques, whereas *Gfap*−/−*Vim*−/− astrocytes showed little process hypertrophy and lacked contact with adjacent plaques; astrocyte density was unchanged.
- Microglial density was slightly higher and microglia–plaque overlap was two-fold greater in APP/PS1 *Gfap*−/−*Vim*−/− mice, but plaque burden still increased.
Methods
- APPswe/PS1ΔE9 transgenic mice were crossed with *Gfap*−/−*Vim*−/− mice over 3 generations to produce APP/PS1 *Gfap*+/+*Vim*+/+ and APP/PS1 *Gfap*−/−*Vim*−/− mice on the same mixed background.
- Brains were analyzed by immunohistochemistry, immunofluorescence, X-34 plaque staining, Aβ ELISA, real-time qPCR, Western blotting, in vivo microdialysis, AAV-GFAP-GFP stereotactic injection, plaque quantification, and unbiased stereology.
- Comparisons used two-tailed Student’s *t* test or Mann-Whitney *U* test; plaque quantification used n=9–10/group, stereology n=5/group, and AAV injection n=3/group.
Limitations
- The paper states that the precise mechanism for the contact-dependent, plaque-suppressing effect is unclear, and that direct evidence for astrocyte phagocytosis of plaque material is lacking.
- The paper states it cannot discount the possibility that activated astrocytes remove dystrophic neurites, meaning the observed changes could reflect impaired clearance rather than exacerbated neurotoxicity.
- Evident from the text: findings are limited to the APP/PS1 mouse model and genetic deletion approach; proposed mechanisms such as delivery of Aβ-degrading proteases or altered vascular Aβ transport were not directly tested.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Verification
Claims the paper makes
40 Own result · 25 Own interpretation · 12 Partly supported · 11 No full text of the sources · 6 Supported · 6 Supported so far · 2 Sources not found · 2 Own method · 1 Not supported · 1 Couldn’t confirm · 1 No basis given · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“but Vim requires a second intermediate filament protein (e.g., nestin or synemin in astrocytes) to form a network (20, 24).”
What the sources say
- Not checked — no full text of the sourcecites [20] 20. Eliasson C., Sahlgren C., Berthold C. H., Stakeberg J., Celis J. E., Betsholtz C., Eriksson J. E., Pekny M. (1999) Intermediate filament protein partnership in astrocytes. J. Biol. Chem. 274, 23996–24006 [DOI] [PubMed] [Google Scholar] source
- Disputedcites [24] 24. Jing R., Wilhelmsson U., Goodwill W., Li L., Pan Y., Pekny M., Skalli O. (2007) Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks. J. Cell Sci. 120, 1267–1277 [DOI] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable in our copy) says that vimentin and GFAP can each polymerize on their own; it is synemin that cannot assemble into intermediate filaments on its own and can copolymerize with vimentin. The claim reverses which protein requires a partner. (LLM, conf=0.91)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Because immunostaining with individual antibodies cannot reveal the full extent of astrocyte morphology (16), we expressed GFP in astrocytes in vivo to observe the complete cellular profile of the cells.”
What the sources say
- Supportedcites [16] 16. Wilhelmsson U., Bushong E. A., Price D. L., Smarr B. L., Phung V., Terada M., Ellisman M. H., Pekny M. (2006) Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc. Natl. Acad. Sci. U. S. A. 103, 17513–17518 [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Abstract says GFAP antibodies reveal the cytoskeleton rather than true cellular morphology, and that dye filling reveals the full three-dimensional shape of astrocytes. These passages support the citing sentence’s reason for using a method that shows the complete cellular profile. Page numbers were not provided in our copy. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Further, the effects of acute central nervous system injury are comparable in Gfap−/−, Vim−/−, and wild-type mice (22, 32).”
What the sources say
- Partly supportedcites [22] 22. Pekny M., Johansson C. B., Eliasson C., Stakeberg J., Wallen A., Perlmann T., Lendahl U., Betsholtz C., Berthold C. H., Frisen J. (1999) Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145, 503–514 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Discussion (Defective CNS Scar Formation) says scar formation after brain or spinal cord injury was comparable in wild-type, GFAP−/−, and vimentin−/− mice. But the Results (Responses to Brain Injury) report weaker, diffuse nestin immunoreactivity after injury in vimentin−/− mice, so the broader claim that the effects of injury were comparable is not fully supported. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [32] 32. Li L., Lundkvist A., Andersson D., Wilhelmsson U., Nagai N., Pardo A. C., Nodin C., Stahlberg A., Aprico K., Larsson K., Yabe T., Moons L., Fotheringham A., Davies I., Carmeliet P., Schwartz J. P., Pekna M., Kubista M., Blomstrand F., Maragakis N., Nilsson M., Pekny M. (2008) Protective role of reactive astrocytes in brain ischemia. J. Cereb. Blood Flow Metab. 28, 468–481 [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Transcriptome profiling of different cell types in mouse brain revealed that astrocytes express high levels of phagocytic genes, including Draper/Megf10 and Mertk/integrin αvβ5, which are involved in engulfing debris coated by specific opsins (60).”
What the sources say
- Supportedcites [60] 60. 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., Thompson W. J., Barres B. A. (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264–278 [DOI] [PMC free article] [PubMed] [Google Scholar] source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The deletion of both genes appears to primarily affect astrocytes (for review, see refs. 15, 53).”
What the sources say
- Not checked — no full text of the sourcecites [15] 15. Pekny M., Nilsson M. (2005) Astrocyte activation and reactive gliosis. Glia 50, 427–434 [DOI] [PubMed] [Google Scholar] source
- Partly supportedcites [53] 53. Pekny M., Pekna M. (2004) Astrocyte intermediate filaments in CNS pathologies and regeneration. J. Pathol. 204, 428–437 [DOI] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The ‘Astrocytes, IFs, and reactive gliosis’ section reports that astrocytes in mice lacking both GFAP and vimentin are completely devoid of intermediate filaments. The ‘Astroglial cells without IFs’ section also reports effects in retinal Müller cells; the review does not establish that astrocytes are affected primarily rather than other cell types. (LLM, conf=0.78)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“We have previously found that the expression of MMP-9 is up-regulated in reactive astrocytes surrounding plaques (61, 62)”
What the sources say
- Supportedcites [61] 61. Yan P., Hu X., Song H., Yin K., Bateman R. J., Cirrito J. R., Xiao Q., Hsu F. F., Turk J. W., Xu J., Hsu C. Y., Holtzman D. M., Lee J. M. (2006) Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J. Biol. Chem. 281, 24566–24574 [DOI] [PubMed] [Google Scholar] source
The Discussion states that the study found increased MMP-9 expression in activated astrocytes surrounding diffuse and compact plaques. The results section and Figure 6 identify MMP-9-positive cells around plaques as reactive astrocytes in the mouse models studied. (LLM, conf=0.94)
- Supportedcites [62] 62. Yin K. J., Cirrito J. R., Yan P., Hu X., Xiao Q., Pan X., Bateman R., Song H., Hsu F. F., Turk J., Xu J., Hsu C. Y., Mills J. C., Holtzman D. M., Lee J. M. (2006) Matrix metalloproteinases expressed by astrocytes mediate extracellular amyloid-beta peptide catabolism. J. Neurosci. 26, 10939–10948 [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Results report increased MMP-9 immunoreactivity in reactive, GFAP-positive astrocytes surrounding amyloid plaques in aged APP/PS1 mice. They also report increased MMP-9 mRNA in plaque-adjacent astrocytes compared with astrocytes distant from plaques and wild-type controls. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“amyloid fibrils may not be effectively degraded (8, 12).”
What the sources say
- Not checked — no full text of the sourcecites [8] 8. Paresce D. M., Ghosh R. N., Maxfield F. R. (1996) Microglial cells internalize aggregates of the Alzheimer's disease amyloid β-protein via a scavenger receptor. Neuron 17, 553–565 [DOI] [PubMed] [Google Scholar] source
- Supportedcites [12] 12. Bolmont T., Haiss F., Eicke D., Radde R., Mathis C. A., Klunk W. E., Kohsaka S., Jucker M., Calhoun M. E. (2008) Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J. Neurosci. 28, 4283–4292 [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Discussion (page unavailable) states that the microglial response is ultimately inefficient at clearing existing amyloid deposits without additional manipulation. It also identifies clearance of existing dense deposits as an unresolved challenge, supporting the hedged claim that microglia may not effectively degrade amyloid fibrils. (LLM, conf=0.86)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, Gfap and Vim gene deletion resulted in a marked increase in dystrophic neurites (2- to 3-fold higher than APP/PS1 Gfap+/+Vim+/+ mice), even after normalization for amyloid load.”
- Also stated in: § RESULTS · plain
“At 12 mo of age, dystrophic neurites were significantly more abundant in APP/PS1 Gfap−/−Vim−/− mice than in APP/PS1 Gfap+/+Vim+/+ mice (Fig. 4A–E).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Histological examination of neurons using cresyl violet staining revealed no qualitative differences in neuronal layers of the cortex or hippocampus (Supplemental Fig. S1).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ISF Aβ half-life was unchanged by deletion of Gfap and Vim (Fig. 3B).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 25
- It may state two separate claims as one. 32
- The quote only partly states this claim. 1
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Absence of GFAP and/or Vim in mice has no major effect under physiological conditions (17–20), reflecting the role of intermediate filament (nanofilament) system as a signaling platform in situations connected with cellular stress (21).”
What the sources say
- Supportedcites [17] 17. Pekny M., Leveen P., Pekna M., Eliasson C., Berthold C. H., Westermark B., Betsholtz C. (1995) Mice lacking glial fibrillary acidic protein display astrocytes devoid of intermediate filaments but develop and reproduce normally. EMBO J. 14, 1590–1598 [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Abstract (p. 1590) reports that mice lacking GFAP developed and reproduced normally, with no detected abnormalities across the functions examined. This supports the GFAP-deficient case in the claim; this paper does not itself test mice lacking vimentin. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [18] 18. Gomi H., Yokoyama T., Fujimoto K., Ikeda T., Katoh A., Itoh T., Itohara S. (1995) Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions. Neuron 14, 29–41 [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [19] 19. Colucci-Guyon E., Portier M. M., Dunia I., Paulin D., Pournin S., Babinet C. (1994) Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell 79, 679–694 [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [20] 20. Eliasson C., Sahlgren C., Berthold C. H., Stakeberg J., Celis J. E., Betsholtz C., Eriksson J. E., Pekny M. (1999) Intermediate filament protein partnership in astrocytes. J. Biol. Chem. 274, 23996–24006 [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [21] 21. Pekny M., Lane E. B. (2007) Intermediate filaments and stress. Exp. Cell Res. 313, 2244–2254 [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Astrocytes are activated in response to acute or chronic central nervous system injury. The activated state is characterized by hypertrophy of proximal processes and up-regulation of the intermediate filament (nanofilament) proteins glial fibrillary acid protein (GFAP) and vimentin (Vim) (15, 16).”
What the sources say
- Not checked — no full text of the sourcecites [15] 15. Pekny M., Nilsson M. (2005) Astrocyte activation and reactive gliosis. Glia 50, 427–434 [DOI] [PubMed] [Google Scholar] source
- Partly supportedcites [16] 16. Wilhelmsson U., Bushong E. A., Price D. L., Smarr B. L., Phung V., Terada M., Ellisman M. H., Pekny M. (2006) Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc. Natl. Acad. Sci. U. S. A. 103, 17513–17518 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Results and Discussion report astrocyte activation after injury and thickening of the main GFAP-containing processes. The introductory passage (labeled Abstract in our copy; page unavailable) reports increased GFAP expression and intermediate filaments in reactive astrocytes, and names vimentin as an intermediate-filament marker, but does not specifically establish vimentin up-regulation. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“For example, increased gliosis induced by brain infusion of lipopolysaccharide (4) or overexpression of the inflammatory cytokine interleukin-6 (5) or interferon-γ (6) markedly reduces amyloid plaque burden.”
What the sources say
- Not checked — no full text of the sourcecites [4] 4. DiCarlo G., Wilcock D., Henderson D., Gordon M., Morgan D. (2001) Intrahippocampal LPS injections reduce Abeta load in APP+PS1 transgenic mice. Neurobiol. Aging 22, 1007–1012 [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [5] 5. Chakrabarty P., Jansen-West K., Beccard A., Ceballos-Diaz C., Levites Y., Verbeeck C., Zubair A. C., Dickson D., Golde T. E., Das P. (2009) Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition. FASEB J. 24, 548–559 [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Supportedcites [6] 6. Chakrabarty P., Ceballos-Diaz C., Beccard A., Janus C., Dickson D., Golde T. E., Das P. (2010) IFN-γ promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice. J. Immunol. 184, 5333–5343 [DOI] [PMC free article] [PubMed] [Google Scholar] source
Citation (6) is attached to the interferon-γ example, not the lipopolysaccharide or interleukin-6 examples. The Discussion reports that interferon-γ expression produced glial activation and reduced amyloid-β deposition in APP transgenic mice; the Results quantify plaque-burden reductions of 70–73% in one experimental paradigm. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Attenuated reactive gliosis in Gfap−/− Vim−/− mice was connected with larger infarctions in a mouse model of focal brain ischemia (32) and facilitated disease progression in a mouse model of Batten's disease (33).”
What the sources say
- Not checked — no full text of the sourcecites [32] 32. Li L., Lundkvist A., Andersson D., Wilhelmsson U., Nagai N., Pardo A. C., Nodin C., Stahlberg A., Aprico K., Larsson K., Yabe T., Moons L., Fotheringham A., Davies I., Carmeliet P., Schwartz J. P., Pekna M., Kubista M., Blomstrand F., Maragakis N., Nilsson M., Pekny M. (2008) Protective role of reactive astrocytes in brain ischemia. J. Cereb. Blood Flow Metab. 28, 468–481 [DOI] [PubMed] [Google Scholar] source
- Supportedcites [33] 33. Macauley S. L., Pekny M., Sands M. S. (2011) The role of attenuated astrocyte activation in infantile neuronal ceroid lipofuscinosis. J. Neurosci. 31, 15575–15585 [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Discussion reports that disease progressed faster in GFAP−/−Vim−/−PPT1−/− mice than in PPT1−/− mice and describes the GFAP/vimentin deficiency as a model of attenuated astrocyte activation. Citation 33 supports the Batten’s-disease portion of the sentence; the focal-ischemia finding is assigned to citation 32. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Interestingly, Gfap−/−Vim−/− mice exhibit better posttraumatic regeneration of neuronal synapses (23) and axons (34), increased baseline and posttraumatic neurogenesis (35), and improved functional recovery after spinal cord trauma (36).”
What the sources say
- Supportedcites [23] 23. Wilhelmsson U., Li L., Pekna M., Berthold C. H., Blom S., Eliasson C., Renner O., Bushong E., Ellisman M., Morgan T. E., Pekny M. (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J. Neurosci. 24, 5016–5021 [DOI] [PMC free article] [PubMed] [Google Scholar] source
This source is cited for the synapse-regeneration portion of the sentence, not the separately cited claims about axons, neurogenesis, or spinal-cord recovery. The Results report that after entorhinal cortex lesion, synaptic complexes increased by 77% in Gfap−/−Vim−/− mice between days 4 and 14, compared with 11% in wild-type mice. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [34] 34. Cho K. S., Yang L., Lu B., Feng Ma H., Huang X., Pekny M., Chen D. F. (2005) Re-establishing the regenerative potential of central nervous system axons in postnatal mice. J. Cell Sci. 118, 863–872 [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [35] 35. Wilhelmsson U., Faiz M., de Pablo Y., Sjoqvist M., Andersson D., Widestrand A., Potokar M., Stenovec M., Smith P. L., Shinjyo N., Pekny T., Zorec R., Stahlberg A., Pekna M., Sahlgren C., Pekny M. (2012) Astrocytes negatively regulate neurogenesis through the Jagged1-mediated Notch pathway. Stem Cells 30, 2320–2329 [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“They also support better integration of neural grafts in the retina (37) and neuronal and astrocyte differentiation of neural stem cells transplanted in the hippocampus (38).”
What the sources say
- Not checked — no full text of the sourcecites [37] 37. Kinouchi R., Takeda M., Yang L., Wilhelmsson U., Lundkvist A., Pekny M., Chen D. F. (2003) Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat. Neurosci. 6, 863–868 [DOI] [PubMed] [Google Scholar] source
- Supportedcites [38] 38. Widestrand A., Faijerson J., Wilhelmsson U., Smith P. L., Li L., Sihlbom C., Eriksson P. S., Pekny M. (2007) Increased neurogenesis and astrogenesis from neural progenitor cells grafted in the hippocampus of GFAP−/− Vim−/− mice. Stem Cells 25, 2619–2627 [DOI] [PubMed] [Google Scholar] source
Citation (38) attaches to the hippocampal transplantation finding, not the retinal-graft finding cited as (37). The Introduction says the study compared neurons and astrocytes differentiated from grafted neural progenitor cells, and the Abstract reports more transplant-derived neurons and astrocytes in GFAP−/−Vim−/− mice than in wild-type controls 35 days after transplantation. The supplied passages do not give page numbers. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, after brain or spinal cord injury, reactive gliosis and the formation of glial scar are attenuated and the healing process is prolonged (22).”
What the sources say
- Partly supportedcites [22] 22. Pekny M., Johansson C. B., Eliasson C., Stakeberg J., Wallen A., Perlmann T., Lendahl U., Betsholtz C., Berthold C. H., Frisen J. (1999) Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145, 503–514 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Results section on spinal cord injury and the Discussion section on defective CNS scar formation report less dense, fissured scars in GFAP−/−vim−/− mice, supporting impaired glial scar formation. The paper does not establish that healing after brain or spinal cord injury was prolonged: its Results say surviving mice’s brain wounds were sealed within three weeks, while the Discussion’s suggestion of slower wound closure concerns a preliminary in vitro assay. It also reports comparable astrocyte numbers and cell proliferation, so attenuated reactive gliosis as a whole is broader than the demonstrated scar defect. Page numbers are unavailable in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“They are completely devoid of intermediate filaments since neither of the other two intermediate filament proteins expressed in reactive astrocytes, nestin and synemin, are able to form intermediate filaments in the absence of both GFAP and Vim (20, 22, 24).”
What the sources say
- Not checked — no full text of the sourcecites [20] 20. Eliasson C., Sahlgren C., Berthold C. H., Stakeberg J., Celis J. E., Betsholtz C., Eriksson J. E., Pekny M. (1999) Intermediate filament protein partnership in astrocytes. J. Biol. Chem. 274, 23996–24006 [DOI] [PubMed] [Google Scholar] source
- Partly supportedcites [22] 22. Pekny M., Johansson C. B., Eliasson C., Stakeberg J., Wallen A., Perlmann T., Lendahl U., Betsholtz C., Berthold C. H., Frisen J. (1999) Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145, 503–514 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The paper reports that GFAP−/−vim−/− astrocytes lack intermediate filaments in both quiescent and reactive states. In the Discussion section on altered nestin expression, it says that nestin fails to form filaments on its own in these astrocytes. Our copy does not address synemin or establish that it cannot form filaments without GFAP and vimentin. (LLM, conf=0.87)
- Supportedcites [24] 24. Jing R., Wilhelmsson U., Goodwill W., Li L., Pan Y., Pekny M., Skalli O. (2007) Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks. J. Cell Sci. 120, 1267–1277 [DOI] [PubMed] [Google Scholar] source
The Introduction (page unavailable) identifies GFAP, vimentin, synemin and nestin as astrocyte intermediate-filament proteins and states that synemin cannot assemble into filaments on its own, resembling nestin. The Discussion (page unavailable) reports no detectable synemin in Gfap−/−Vim−/− reactive astrocytes and markedly reduced nestin. Together, these passages support the explanation that nestin and synemin cannot form filaments in the double-knockout astrocytes. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“On a cellular level, astrocytes of Gfap−/−Vim−/− mice in the injured area do not develop the characteristic hypertrophy of proximal processes (23).”
What the sources say
- Supportedcites [23] 23. Wilhelmsson U., Li L., Pekna M., Berthold C. H., Blom S., Eliasson C., Renner O., Bushong E., Ellisman M., Morgan T. E., Pekny M. (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J. Neurosci. 24, 5016–5021 [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Figure 1 caption states that, after entorhinal cortex lesion, wild-type astrocytic processes became hypertrophic whereas those in GFAP−/− Vim−/− mice did not. The Results (Fig. 1) also report shorter reactive astrocytic processes on the lesioned side in the double-knockout mice. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“More recent studies in transgenic mouse models of AD have shown that microglia migrate to amyloid plaques and may alter plaque growth dynamics (9–12).”
What the sources say
- Partly supportedcites [9] 9. Mandrekar S., Jiang Q., Lee C. Y., Koenigsknecht-Talboo J., Holtzman D. M., Landreth G. E. (2009) Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis. J. Neurosci. 29, 4252–4262 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reports that microglia play a role in plaque dynamics in an AD transgenic mouse model and internalize plaque fragments. It does not say that microglia migrate to plaques, so that part of the citing sentence is not supported by this source. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [10] 10. Jiang Q., Lee C. Y., Mandrekar S., Wilkinson B., Cramer P., Zelcer N., Mann K., Lamb B., Willson T. M., Collins J. L., Richardson J. C., Smith J. D., Comery T. A., Riddell D., Holtzman D. M., Tontonoz P., Landreth G. E. (2008) ApoE promotes the proteolytic degradation of Abeta. Neuron 58, 681–693 [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Supportedcites [11] 11. Meyer-Luehmann M., Spires-Jones T. L., Prada C., Garcia-Alloza M., de Calignon A., Rozkalne A., Koenigsknecht-Talboo J., Holtzman D. M., Bacskai B. J., Hyman B. T. (2008) Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 451, 720–724 [DOI] [PMC free article] [PubMed] [Google Scholar] source
In the Abstract, the authors report that microglia were attracted to newly formed plaques within a day in APP transgenic mice. They also suggest that microglia may restrict plaque growth, matching the claim’s qualified wording. (LLM, conf=0.93)
- Supportedcites [12] 12. Bolmont T., Haiss F., Eicke D., Radde R., Mathis C. A., Klunk W. E., Kohsaka S., Jucker M., Calhoun M. E. (2008) Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J. Neurosci. 28, 4283–4292 [DOI] [PMC free article] [PubMed] [Google Scholar] source
The Abstract reports that microglia migrate toward plaques in transgenic mice and that changes in plaque size are related to the volume of associated microglia. The Microglial migration section describes cells moving to plaque peripheries over 24–48 hours. The claim's cautious wording, “may alter,” is consistent with these findings. (LLM, conf=0.93)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“But when Gfap and Vim are both deleted, astrocytes cannot form intermediate filament networks or display reactive morphology (22, 23, 32).”
What the sources say
- Partly supportedcites [22] 22. Pekny M., Johansson C. B., Eliasson C., Stakeberg J., Wallen A., Perlmann T., Lendahl U., Betsholtz C., Berthold C. H., Frisen J. (1999) Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145, 503–514 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) says GFAP−/−vim−/− astrocytes cannot form intermediate filaments, even in their reactive state. The Discussion (page unavailable) reports defective scar formation and suggests reduced astrocytic process formation, but does not establish that these astrocytes cannot display reactive morphology at all. (LLM, conf=0.88)
- Partly supportedcites [23] 23. Wilhelmsson U., Li L., Pekna M., Berthold C. H., Blom S., Eliasson C., Renner O., Bushong E., Ellisman M., Morgan T. E., Pekny M. (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J. Neurosci. 24, 5016–5021 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Introduction says GFAP/Vim-deficient astrocytes are completely devoid of intermediate filaments. But the Results and Figure 1 describe them as reactive astrocytes with altered morphology and limited process hypertrophy, not as unable to display any reactive morphology. Page numbers are not available in the supplied copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [32] 32. Li L., Lundkvist A., Andersson D., Wilhelmsson U., Nagai N., Pardo A. C., Nodin C., Stahlberg A., Aprico K., Larsson K., Yabe T., Moons L., Fotheringham A., Davies I., Carmeliet P., Schwartz J. P., Pekna M., Kubista M., Blomstrand F., Maragakis N., Nilsson M., Pekny M. (2008) Protective role of reactive astrocytes in brain ischemia. J. Cereb. Blood Flow Metab. 28, 468–481 [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In several models of acute central nervous system injury, deletion of the genes encoding these proteins suppresses morphological changes associated with astrocyte activation (22, 23, 26, 30, 32, 36).”
What the sources say
- Partly supportedcites [22] 22. Pekny M., Johansson C. B., Eliasson C., Stakeberg J., Wallen A., Perlmann T., Lendahl U., Betsholtz C., Berthold C. H., Frisen J. (1999) Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145, 503–514 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Abstract and Discussion report impaired, less compact glial scars after brain and spinal cord injury in mice lacking both GFAP and vimentin. This supports an altered injury-associated morphology, but the paper does not show that astrocyte activation’s morphological changes are suppressed generally; it reports a normal injury-induced proliferation response and treats reduced astrocytic process formation as a possible explanation for the scar defect. (LLM, conf=0.82)
- Supportedcites [23] 23. Wilhelmsson U., Li L., Pekna M., Berthold C. H., Blom S., Eliasson C., Renner O., Bushong E., Ellisman M., Morgan T. E., Pekny M. (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J. Neurosci. 24, 5016–5021 [DOI] [PMC free article] [PubMed] [Google Scholar] source
This paper supplies one of the injury models covered by the sentence’s multiple citations. In the entorhinal cortex lesion model, Figure 1 reports that GFAP/Vim-deficient mice did not develop the astrocytic process hypertrophy seen in wild-type mice (pp. 5016–5021). (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [26] 26. Lu Y. B., Iandiev I., Hollborn M., Korber N., Ulbricht E., Hirrlinger P. G., Pannicke T., Wei E. Q., Bringmann A., Wolburg H., Wilhelmsson U., Pekny M., Wiedemann P., Reichenbach A., Kas J. A. (2011) Reactive glial cells: increased stiffness correlates with increased intermediate filament expression. FASEB J. 25, 624–631 [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Previous work has shown BDNF expression is increased in amyloid-associated astrocytes (51)”
What the sources say
- Supportedcites [51] 51. Burbach G. J., Hellweg R., Haas C. A., Del Turco D., Deicke U., Abramowski D., Jucker M., Staufenbiel M., Deller T. (2004) Induction of brain-derived neurotrophic factor in plaque-associated glial cells of aged APP23 transgenic mice. J. Neurosci. 24, 2421–2430 [DOI] [PMC free article] [PubMed] [Google Scholar] source
The section on plaque-associated astroglial and microglial cells reports numerous BDNF-positive astrocytes around amyloid plaques, while astroglial cells in plaque-free areas were BDNF-negative. This supports increased BDNF expression in amyloid-associated astrocytes in the APP23 mouse model studied. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“and that MMP-9 is capable of degrading amyloid fibrils in vitro and amyloid plaques in situ (61).”
What the sources say
- Supportedcites [61] 61. Yan P., Hu X., Song H., Yin K., Bateman R. J., Cirrito J. R., Xiao Q., Hsu F. F., Turk J. W., Xu J., Hsu C. Y., Holtzman D. M., Lee J. M. (2006) Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J. Biol. Chem. 281, 24566–24574 [DOI] [PubMed] [Google Scholar] source
The paper reports that MMP-9 degrades amyloid-β fibrils in vitro. Its Discussion also states that MMP-9 degrades compact amyloid plaques in brain sections from aged APP/PS1 mice, supporting the in situ part of the claim. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Under baseline conditions, however, Gfap−/−Vim−/− mice have astrocytes of normal appearance and grossly normal brain anatomy (22, 23, 32).”
What the sources say
- Partly supportedcites [22] 22. Pekny M., Johansson C. B., Eliasson C., Stakeberg J., Wallen A., Perlmann T., Lendahl U., Betsholtz C., Berthold C. H., Frisen J. (1999) Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145, 503–514 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
Materials and Methods (Animals; page not available) says the double-mutant mice reached adulthood without overt anatomical defects, supporting the broad claim of grossly normal anatomy. Our copy does not establish that their astrocytes appeared normal under baseline conditions. Results (Dilated Blood Vessels; page not available) also documents abnormalities in the uninjured brain and spinal cord, so grossly normal should not be read as anatomically unchanged. (LLM, conf=0.86)
- Partly supportedcites [23] 23. Wilhelmsson U., Li L., Pekna M., Berthold C. H., Blom S., Eliasson C., Renner O., Bushong E., Ellisman M., Morgan T. E., Pekny M. (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J. Neurosci. 24, 5016–5021 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
Figure 1 and the Results (page not specified in our copy) report similar astrocyte morphology and process length in GFAP−/− Vim−/− and wild-type mice before lesion. The paper does not establish the broader claim that their brain anatomy is grossly normal. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [32] 32. Li L., Lundkvist A., Andersson D., Wilhelmsson U., Nagai N., Pardo A. C., Nodin C., Stahlberg A., Aprico K., Larsson K., Yabe T., Moons L., Fotheringham A., Davies I., Carmeliet P., Schwartz J. P., Pekna M., Kubista M., Blomstrand F., Maragakis N., Nilsson M., Pekny M. (2008) Protective role of reactive astrocytes in brain ischemia. J. Cereb. Blood Flow Metab. 28, 468–481 [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The intermediate filament proteins GFAP and Vim are expressed at high levels in activated astrocytes and are critical for the activated phenotype.”
What the sources say
- Partly supportedcites [22] 22. Pekny M., Johansson C. B., Eliasson C., Stakeberg J., Wallen A., Perlmann T., Lendahl U., Betsholtz C., Berthold C. H., Frisen J. (1999) Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145, 503–514 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The paper’s Abstract (page not provided) states that astrocytes express high levels of GFAP and vimentin after CNS injury. It also reports that losing both proteins impairs glial scar formation, but it does not establish that they are critical for the activated phenotype as a whole: the double-deficient astrocytes are described as reactive, and the Discussion reports a normal proliferation response to injury. (LLM, conf=0.88)
- Partly supportedcites [23] 23. Wilhelmsson U., Li L., Pekna M., Berthold C. H., Blom S., Eliasson C., Renner O., Bushong E., Ellisman M., Morgan T. E., Pekny M. (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J. Neurosci. 24, 5016–5021 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Introduction describes intermediate-filament upregulation as a hallmark of reactive astrocytes and proposes that it is crucial to activation. Figure 1 and the Results show that loss of GFAP and vimentin prevents process hypertrophy and endothelin B receptor upregulation after injury. The paper still calls the deficient astrocytes reactive, so it supports a role in specific features of the activated phenotype, not that these proteins are critical to the activated phenotype as a whole. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [32] 32. Li L., Lundkvist A., Andersson D., Wilhelmsson U., Nagai N., Pardo A. C., Nodin C., Stahlberg A., Aprico K., Larsson K., Yabe T., Moons L., Fotheringham A., Davies I., Carmeliet P., Schwartz J. P., Pekna M., Kubista M., Blomstrand F., Maragakis N., Nilsson M., Pekny M. (2008) Protective role of reactive astrocytes in brain ischemia. J. Cereb. Blood Flow Metab. 28, 468–481 [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Astrocyte endfeet line the abluminal aspect of endothelial cells and are important for the formation and maintenance of the blood-brain-barrier (29).”
What the sources say
- Could not verifycites [29] 29. Vardjan N., Gabrijel M., Potokar M., Svajger U., Kreft M., Jeras M., de Pablo Y., Faiz M., Pekny M., Zorec R. (2012) IFN-gamma-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments. J. Neuroinflammation 9, 144. [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Background and Conclusions discuss astrocyte antigen presentation and MHC class II trafficking, not astrocyte endfeet or the blood–brain barrier. Searches for endfeet, endothelial cells, and blood–brain barrier formation and maintenance found no passage addressing the claim in our copy. (LLM, conf=0.75)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Although microglia can internalize fibrillar Aβ in vitro and in vivo”
What the sources say
- Not checked — no full text of the sourcecites [8] 8. Paresce D. M., Ghosh R. N., Maxfield F. R. (1996) Microglial cells internalize aggregates of the Alzheimer's disease amyloid β-protein via a scavenger receptor. Neuron 17, 553–565 [DOI] [PubMed] [Google Scholar] source
- Partly supportedcites [12] 12. Bolmont T., Haiss F., Eicke D., Radde R., Mathis C. A., Klunk W. E., Kohsaka S., Jucker M., Calhoun M. E. (2008) Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J. Neurosci. 28, 4283–4292 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Introduction says microglia can phagocytose Aβ in culture, and the ‘Microglia uptake of injected dye’ section reports Aβ-positive particles inside microglia in vivo. But the Discussion explicitly says further study is needed to determine whether the internalized material is soluble Aβ or fibrillary amyloid. The source therefore supports Aβ uptake in both settings, not the claim that fibrillar Aβ is internalized in vivo. Page numbers are unavailable in our copy. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Moreover, astrocytes may play an important role in the transport of Aβ into or out of the CNS through this important interface (63).”
What the sources say
- Partly supportedcites [63] 63. Askarova S., Yang X., Sheng W., Sun G. Y., Lee J. C. (2011) Role of Abeta-receptor for advanced glycation endproducts interaction in oxidative stress and cytosolic phospholipase A(2) activation in astrocytes and cerebral endothelial cells. Neuroscience 199, 375–385 [DOI] [PMC free article] [PubMed] [Google Scholar] sourceExperimental — accuracy not yet measured
The Introduction (page not available) says Aβ binding to RAGE regulates transport across the blood–brain barrier, and the paper identifies astrocytes as a component of that barrier. It does not say that astrocytes themselves transport Aβ into or out of the CNS through the astrocyte–vasculature interface. (LLM, conf=0.83)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“APP expression and soluble and interstitial fluid Aβ levels were unchanged, suggesting that the deletions had no effect on APP processing or Aβ generation.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Astrocyte morphology was markedly altered by the deletions: wild-type astrocytes had hypertrophied processes that surrounded and infiltrated plaques, whereas Gfap−/−Vim−/− astrocytes had little process hypertrophy and lacked contact with adjacent plaques.”
- Also stated in: § RESULTS · plain
“Astrocytic invasion of plaques is attenuated in APP/PS1 Gfap−/−Vim−/− mice”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The gene deletions increased amyloid plaque load: APP/PS1 Gfap−/−Vim−/− mice had twice the plaque load of APP/PS1 Gfap+/+Vim+/+ mice at 8 and 12 mo of age.”
- Also stated in: § RESULTS · plain
“Aβ load and amyloid load were significantly increased in the cortex and hippocampus of APP/PS1 Gfap−/−Vim−/− mice at 8 and 12 but not 4 mo of age (Fig. 1A–F).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § RESULTS · plain
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Mice of both genotypes were grossly normal and fertile, without obvious behavioral or anatomical differences.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 8 and 12 mo, APP/PS1 Gfap−/− Vim−/− mice had significantly higher Aβ levels in the guanidine extract but not in the PBS fraction (Fig. 2).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Only APH-1b and MMP-9 showed significant, but modest, decreases (20-30% decrease) in mRNA levels in the APP/PS1 Gfap−/−Vim−/− mice (Fig. 5A); transcript levels for all other genes were unchanged.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although Gfap/Vim gene deletion exacerbates neuritic dystrophy, we observed no difference in the pattern of synaptophysin immunoreactivity surrounding plaques and no difference in the amount of synaptophysin or PSD95 mRNA between the cortices of each genotype (Supplemental Fig. S3).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, MMP-2 and MMP-9 showed no significant changes in APP/PS1 Gfap−/−Vim−/− mice (Fig. 5D, E), although pro-MMP9 and MMP9 showed a decreasing trend.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ApoE and apoJ (clusterin) showed no significant differences (Fig. 5C, E).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, astrocytes from APP/PS1 Gfap−/−Vim−/− mice did not exhibit process hypertrophy, and distal processes appeared as fine strands.”
- Also stated in: § DISCUSSION · plain
“Gfap−/−Vim−/− astrocytes lacked the hypertrophic processes observed in wild-type astrocytes.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § DISCUSSION · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“APP expression and soluble and interstitial fluid Aβ levels were unchanged, suggesting that the deletions had no effect on APP processing or Aβ generation.”
- Also stated in: § RESULTS · hedged
“Western blot analysis showed no differences between genotypes in APP expression and C-terminal fragments (Fig. 5B, E), suggesting that Gfap and Vim gene deletion did not alter APP expression or processing.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § RESULTS · hedged
In the paper
“In 2003, Wyss-Coray et al. (41) demonstrated that cultured adult astrocytes can migrate to and degrade amyloid plaques in brain slices from aged APP transgenic mice.”
What the sources say
- Not checked — no full text of the sourcecites [41] 41. Wyss-Coray T., Loike J. D., Brionne T. C., Lu E., Anankov R., Yan F., Silverstein S. C., Husemann J. (2003) Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat. Med. 9, 453–457 [DOI] [PubMed] [Google Scholar] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“In vitro studies subsequently demonstrated that microglia can internalize and clear Aβ (8).”
What the sources say
- Not checked — no full text of the sourcecites [8] 8. Paresce D. M., Ghosh R. N., Maxfield F. R. (1996) Microglial cells internalize aggregates of the Alzheimer's disease amyloid β-protein via a scavenger receptor. Neuron 17, 553–565 [DOI] [PubMed] [Google Scholar] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, near-complete ablation of microglia in transgenic mice expressing mutant human amyloid precursor protein (APP) and presenilin 1 (PS1) had no effect on plaque deposition or neuritic dystrophy (13), raising questions about the role of endogenous microglia in plaque clearance.”
What the sources say
- Not matchedcites [13] 13. Grathwohl S. A., Kalin R. E., Bolmont T., Prokop S., Winkelmann G., Kaeser S. A., Odenthal J., Radde R., Eldh T., Gandy S., Aguzzi A., Staufenbiel M., Mathews P. M., Wolburg H., Heppner F. L., Jucker M. (2009) Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the absence of microglia. Nat. Neurosci. 12, 1361–1363 [DOI] [PMC free article] [PubMed] [Google Scholar]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gfap/Vim deletion does not alter expression or processing of APP or Aβ-degrading proteases”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Early ultrastructural studies in human brain specimens suggested that microglia can engulf amyloid-β (Aβ) and sequester it in endosome-like compartments (7).”
What the sources say
- Not checked — no full text of the sourcecites [7] 7. Frackowiak J., Wisniewski H. M., Wegiel J., Merz G. S., Iqbal K., Wang K. C. (1992) Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce β-amyloid fibrils. Acta Neuropathol. 84, 225–233 [DOI] [PubMed] [Google Scholar] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that Gfap and Vim deletion selectively alters insoluble (plaque-associated) Aβ but not the soluble pools of Aβ in APP/PS1 mice.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In general, APP transgenic mice do not show significant neuronal cell death or brain atrophy, in contrast to brains of patients with AD (49).”
What the sources say
- Not checked — no full text of the sourcecites [49] 49. Irizarry M. C., McNamara M., Fedorchak K., Hsiao K., Hyman B. T. (1997) APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1. J. Neuropathol. Exp. Neurol. 56, 965–973 [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Mice of both genotypes were maintained on the same mixed backgrounds (B6C3 × C57BL 129SV 129Ola).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that activated astrocytes either protect neurons from developing dystrophic neurites or are involved in the clearance of dystrophyic neurites.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, Gfap and Vim deletion does not alter ISF Aβ levels or metabolism but selectively alters amyloid plaque load.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that Gfap and Vim deletions do not influence the initial deposition of plaques but exacerbate subsequent plaque accumulation, consistent with the contention that Gfap/Vim deletion selectively affects astrocyte activation—an event that occurs after initial plaque formation.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: In APP/PS1 mice, plaque accumulation begins at about 4 months of age and increases thereafter.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that Gfap and Vim deletions do not influence the initial deposition of plaques but exacerbate subsequent plaque accumulation, consistent with the contention that Gfap/Vim deletion selectively affects astrocyte activation—an event that occurs after initial plaque formation.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: In APP/PS1 mice, plaque accumulation begins at about 4 months of age and increases thereafter.
In the paper
“Moreover, this plaque-degrading activity in astrocytes was subsequently found to be dependent on apolipoprotein E (apoE) expression (42).”
What the sources say
- Not checked — no full text of the sourcecites [42] 42. Koistinaho M., Lin S., Wu X., Esterman M., Koger D., Hanson J., Higgs R., Liu F., Malkani S., Bales K. R., Paul S. M. (2004) Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides. Nat. Med. 10, 719–726 [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“and Aβ has been observed in vesicles within astrocytes (57, 58).”
What the sources say
- Not checked — no full text of the sourcecites [57] 57. Yamaguchi H., Sugihara S., Ogawa A., Saido T. C., Ihara Y. (1998) Diffuse plaques associated with astroglial amyloid β-protein, possibly showing a disappearing stage of senile plaques. Acta Neuropathol. 95, 217–222 [DOI] [PubMed] [Google Scholar] source
- Not checked — no full text of the sourcecites [58] 58. Thal D. R., Schultz C., Dehghani F., Yamaguchi H., Braak H., Braak E. (2000) Amyloid β-protein (Abeta)-containing astrocytes are located preferentially near N-terminal-truncated Abeta deposits in the human entorhinal cortex. Acta Neuropathol. 100, 608–617 [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the major change induced by Gfap and Vim gene deletion appeared to be morphology of activated astrocytes without any major transcriptional change identified.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“and that this may play a role in amyloid associated pathology (52).”
What the sources say
- Not checked — no full text of the sourcecites [52] 52. Szapacs M. E., Numis A. L., Andrews A. M. (2004) Late onset loss of hippocampal 5-HT and NE is accompanied by increases in BDNF protein expression in mice co-expressing mutant APP and PS1. Neurobiol. Dis. 16, 572–580 [DOI] [PubMed] [Google Scholar] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, individual deletion of Gfap or Vim allows formation of intermediate filament networks and astrocyte activation under pathological conditions.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that deletion of Gfap and Vim alters the activation and morphology of astrocytes without altering their viability.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Astrocyte density (GFP-expressing or glutamine synthetase-immunostained) is a valid measure of astrocyte viability.
In the paper
“Furthermore, near-complete ablation of microglia in APP mice does not alter plaque load (13).”
What the sources say
- Not matchedcites [13] 13. Grathwohl S. A., Kalin R. E., Bolmont T., Prokop S., Winkelmann G., Kaeser S. A., Odenthal J., Radde R., Eldh T., Gandy S., Aguzzi A., Staufenbiel M., Mathews P. M., Wolburg H., Heppner F. L., Jucker M. (2009) Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the absence of microglia. Nat. Neurosci. 12, 1361–1363 [DOI] [PMC free article] [PubMed] [Google Scholar]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Astrocytes support neuronal function by regulating extracellular concentrations of ions and neurotransmitters (65), especially in response to cellular stress (21).”
What the sources say
- Not checked — no full text of the sourcecites [65] 65. Allen N. J., Barres B. A. (2009) Neuroscience: Glia - more than just brain glue. Nature 457, 675–677 [DOI] [PubMed] [Google Scholar] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. source
- Not checked — no full text of the sourcecites [21] 21. Pekny M., Lane E. B. (2007) Intermediate filaments and stress. Exp. Cell Res. 313, 2244–2254 [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Direct evidence that reactive gliosis suppresses plaque accumulation is lacking.
“However, direct evidence that reactive gliosis suppresses plaque accumulation is lacking.”
The paper relies on this without support.
In APP/PS1 mice, plaque accumulation begins at about 4 months of age and increases thereafter.
“In APP/PS1 mice, plaque accumulation begins at ∼4 mo of age and increases thereafter.”
The paper relies on this without support.
The role of reactive astrocytes in Alzheimer's disease pathogenesis is unclear.
“Reactive astrocytes are intimately associated with amyloid plaques; however, their role in AD pathogenesis is unclear.”
The paper relies on this without support.
With the exception of Batten's disease, the role of astrocyte intermediate filament proteins in chronic neurodegenerative diseases has not been investigated.
“With the exception of Batten's disease (33), the role of astrocyte intermediate filament proteins in chronic neurodegenerative diseases has not been investigated.”
The paper relies on this without support.
X-34 staining specifically and quantitatively identifies amyloid plaques.
“Processes were also evident deep within X-34-stained plaques, suggesting process invasion within plaques (Fig. 6C).”
The paper relies on this without support.
GFP expression driven by the Gfap promoter specifically labels astrocytes and reveals their complete morphology.
“mice were injected with AAV2 constructs carrying GFP driven by a Gfap promoter (AAV-GFAP-GFP)”
“we expressed GFP in astrocytes in vivo to observe the complete cellular profile of the cells”
The paper relies on this without support.
Astrocyte density (GFP-expressing or glutamine synthetase-immunostained) is a valid measure of astrocyte viability.
“suggesting that deletion of Gfap and Vim alters the activation and morphology of astrocytes without altering their viability.”
The paper relies on this without support.
The increase in amyloid plaque load in APP/PS1 Gfap−/−Vim−/− mice is due to attenuated astrocyte activation rather than other effects of Gfap/Vim deletion.
“In summary, our studies demonstrate that reactive gliosis around amyloid plaques is important for restricting the appearance and growth of amyloid plaques in APP mice.”
The paper relies on this without support.
Microglial density and plaque overlap reflect microglial recruitment, proliferation, or function around plaques.
“Thus, microglia seem to be more abundant around plaques in the absence of activated astrocytes.”
The paper relies on this without support.
Gene expression levels measured by quantitative PCR reflect functional protein activity.
“Quantitative PCR analysis revealed no difference in BDNF message levels (Supplemental Fig. S3G).”
“Real-time PCR from the cortex of 12-mo-old mice confirmed an increased gene expression of CD11b and Iba-1 in APP/PS1 Gfap−/−Vim−/− mice”
The paper relies on this without support.
The measured half-life of ISF Aβ is representative of Aβ metabolism relevant to plaque pathogenesis.
“and the half-life of ISF Aβ was unchanged.”
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 doesn’t support the claim as written.
In the citing paper
“Therefore, it seems that the consensus is that the reduction in astrocyte density leads to higher amyloid levels, without changes in its aggregation or deposition.”
From Pharmacological ablation of astrocytes reduces Aβ degradation and synaptic connectivity in an ex vivo model of Alzheimer’s disease (2021) · cites this paper as [29]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“We also observed that our astrocyte population in the CNO group did not show the transcriptional profile of reactive astrogliosis that is typically seen in neurodegenerative diseases (Supplementary Figure 2D) (Kraft et al., 2013).”
From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Kraft et al., 2013
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It has been demonstrated that GFAP knockout results in an increase in A β load, thereby implicating the filament protein that is required for astrocyte activation in the response to AD pathology (Kraft et al., 2013).”
From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Kraft et al., 2013
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“reactive astrocytes have been reported to phagocytose and degrade Aβ, reducing Aβ plaque burden in the brain (Wyss-Coray et al., 2003;Koistinaho et al., 2004;Kraft et al., 2013;Gomez-Arboledas et al., 2018;Preman et al., 2021)”
From Cell Adhesion Molecule Protocadherin-γC5 Ameliorates Aβ Plaque Pathogenesis by Modulating Astrocyte Function in Alzheimer's Disease (2025) · cites this paper as Kraft et al., 2013
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Moreover, astrocytes can also modulate microglial responses to Aβ [55, 58, 59].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [55]
The cited source says what the claim attributes to it.
In the citing paper
“astrocytes have been shown to restrict amyloid pathology [55–57].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [55]
The cited source says what the claim attributes to it.
In the citing paper
“For example, the manipulation of reactive astrocytes has resulted in improved outcomes38,42,43, worse35 outcomes, and no change44 in mouse models of AD and MS40,45,46.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [35]
In the citing paper
“However, astrocytes are immune-competent. They respond to a wide range of brain insults and are activated in a wide range of neurodegenerative diseases including Alzheimer’s disease9,69–71.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [70]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ RESULTS
“Only APH-1b and MMP-9 showed significant, but modest, decreases (20-30% decrease) in mRNA levels in the APP/PS1 Gfap−/−Vim−/− mice (Fig. 5A); transcript levels for all other genes were unchanged.”
§ DISCUSSION
“Although we did not find significant differences in the expression of Aβ-degrading proteases or Aβ-binding chaperones (apoE and apoJ) expressed by astrocytes, it is plausible that their direct delivery into or around nascent plaques was impaired in the Gfap−/−Vim−/− astrocytes”
Citations
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Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
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Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
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Astrocyte activation and reactive gliosis
Pekny, M., & Nilsson, M. (2005) · Glia · doi:10.1002/glia.20207 · Cited by 1,611
Self-citationJankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575
The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease
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Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284
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Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease
Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J., & Hyman, B. T. (2008) · Nature · doi:10.1038/nature06616 · Cited by 987
Self-citationSTAT3 is a Critical Regulator of Astrogliosis and Scar Formation after Spinal Cord Injury
Herrmann, J. E., Imura, T., Song, B., Qi, J., Ao, Y., Nguyen, T. K., Korsak, R. A., Takeda, K., Akira, S., & Sofroniew, M. V. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1709-08.2008 · Cited by 958
Cited by
Sorted by citations
Items 101–200 of 324
Findlay, C. R. J., Rak, M., Lund, J., Unger, M. V., Platt, E., Albensi, B. C., Hirschmugl, C. J., & Gough, K. M. (2013) · The Analyst · doi:10.1039/c3an00295k · Cited by 85
Neutralization of TNFSF10 ameliorates functional outcome in a murine model of Alzheimer’s disease
Cantarella, G., Benedetto, G. D., Puzzo, D., Privitera, L., Loreto, C., Saccone, S., Giunta, S., Palmeri, A., & Bernardini, R. (2014) · Brain · doi:10.1093/brain/awu318 · Cited by 87
“…which seem relevant to Alzheimer’s disease (Avila-Muñoz and Arias, 2014), are constantly present in the brain of patients with Alzheimer’s disease (Kraft et al., 2013), and amyloid-b accumulates (Veeraraghavalu et al., 2014) and can induce morphological changes (Nagele et al., 2003) in these…”
Lv, Y.-Q., Yuan, L., Sun, Y., Dou, H.-W., Su, J.-H., Hou, Z.-P., Li, J.-Y., & Li, W. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00288-z · Cited by 82
“In the process of neuroinflammation, theoretically the loss of astroglia and the disrupted integrity of astrogliosis could be harmful, as the neuroprotective roles of the cells are no longer present [64].”
BackgroundAstrocytes: Heterogeneous and Dynamic Phenotypes in Neurodegeneration and Innate Immunity
Cunningham, C. M., Dunne, A., & López-Rodríguez, A. B. (2018) · The Neuroscientist · doi:10.1177/1073858418809941 · Cited by 80
Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer's disease
Katsouri, L., Birch, A. M., Renziehausen, A. W. J., Zach, C., Aman, Y., Steeds, H., Bonsu, A., Palmer, E. O. C., Mirzaei, N., Ries, M., et al. (2020) · Glia · doi:10.1002/glia.23759 · Cited by 81
Merlo, S., Spampinato, S. F., & Sortino, M. A. (2018) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13050 · Cited by 82
Landel, V., Millet, P., Baranger, K., Loriod, B., & Feron, F. P. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0087-2 · Cited by 77
“However, we cannot rule out that, at the same time, gliosis affects the synaptic and metabolic support functions of astrocytes [116, 117].”
BackgroundIdentification of Conserved Proteomic Networks in Neurodegenerative Dementia
Swarup, V., Chang, T. S., Duong, D. M., Dammer, E. B., Dai, J., Lah, J. J., Johnson, E. C. B., Seyfried, N. T., Levey, A. I., & Geschwind, D. H. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107807 · Cited by 78
“In vivo studies have been contradictory as AD mice lacking GFAP and VIM had both increased Aβ in one study (Kraft et al., 2013) and no change in amyloid β staining in another (Kamphuis et al., 2015).”
BackgroundIdentification of conserved proteomic networks in neurodegenerative dementia
Swarup, V., Chang, T. S., Duong, D. M., Dammer, E. B., Lah, J. J., Johnson, E. E. C. B., Seyfried, N. T., Levey, A. I., & Geschwind, D. H. (2019) · doi:10.1101/825802 · Cited by 78
Chun, H., Marriott, I., Lee, C. J., & Cho, H. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00797 · Cited by 77
“Such findings indicate that activationassociated changes in astrocyte morphology limit Aβ plaque growth and attenuate plaque-related dystrophic neurites (60, 61).”
BackgroundDeng, X., Li, M., Ai, W., He, L., Lu, D., Patrylo, P. R., Cai, H., Luo, X., Li, Z., & Yan, X. (2014) · Advances in Alzheimer s Disease · doi:10.4236/aad.2014.32009 · Cited by 73
Rivera-Escalera, F., Pinney, J. J., Owlett, L., Ahmed, H., Thakar, J., Olschowka, J. A., Elliott, M. R., & O’Banion, M. K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1645-7 · Cited by 75
Li, M., Ji, J., Zheng, L.-J., Shen, J., Li, X., Zhang, Q., Bai, X., & Wang, Q. (2018) · Neural Regeneration Research · doi:10.4103/1673-5374.239449 · Cited by 74
“Attenuating astrocyte activation can accelerate plaque pathogenesis in amyloid precursor protein/presenilin RESEARCH ARTICLE 1 (APP/PS1) mice (Kraft et al., 2013).”
BackgroundGoetzl, E. J., Yaffe, K. S., Peltz, C. B., Ledreux, A., Gorgens, K. A., Davidson, B. S., Granholm, A., Mustapić, M., Kapogiannis, D., Tweedie, D., et al. (2020) · The FASEB Journal · doi:10.1096/fj.201902842r · Cited by 74
Norden, D. M., Trojanowski, P. J., Walker, F. R., & Godbout, J. P. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.014 · Cited by 73
Genetic deletion of soluble epoxide hydrolase delays the progression of Alzheimer’s disease
Lee, H., Lee, K.-I., Chen, C.-H., & Lee, T. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1635-9 · Cited by 69
Smit, T., Deshayes, N. A. C., Borchelt, D. R., Kamphuis, W., Middeldorp, J., & Hol, E. M. (2021) · Glia · doi:10.1002/glia.23981 · Cited by 71
van Gijsel-Bonnello, M., Baranger, K., Benech, P., Rivera, S., Khrestchatisky, M., de Reggi, M., & Gharib, B. (2017) · PLOS ONE · doi:10.1371/journal.pone.0175369 · Cited by 63
“It can be objected that attenuation of astrocyte reactivity could have adverse effects in AD by accelerating plaque growth, as previously shown [3].”
ResultBolton-Hall, A. N., Joseph, B., Brelsfoard, J., & Saatman, K. E. (2016) · PLoS ONE · doi:10.1371/journal.pone.0159442 · Cited by 72
“Such an inverse relationship between the activation of astrocytes and of microglia has been reported in mouse models of Alzheimer’s disease [68] and Batten disease [69].”
BackgroundThe role of GFAP and vimentin in learning and memory
Wilhelmsson, U., Pozo-Rodrigálvarez, A., Kalm, M., de Pablo, Y., Widestrand, Å., Pekna, M., & Pekny, M. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0199 · Cited by 65
Self-citationAlzheimer's Disease and Sleep–Wake Disturbances: Amyloid, Astrocytes, and Animal Models
Vanderheyden, W. M., Lim, M. M., Musiek, E. S., & Gerstner, J. R. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1135-17.2017 · Cited by 64
The leukotriene signaling pathway: a druggable target in Alzheimer’s disease
Michael, J., Marschallinger, J., & Aigner, L. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.09.008 · Cited by 70
“Astrocytes associated with amyloid plaques are phagocytotic, and take up and degrade A b [42] and/or prevent plaque formation or plaquegrowth [43].”
BackgroundThe role of microglia in the development of neurodegeneration
Saitgareeva, A. R., Bulygin, K. V., Фанилевич, Г. И., Beylerli, O., & Ахмадеева, Л. Р. (2020) · Neurological Sciences · doi:10.1007/s10072-020-04468-5 · Cited by 67
Davis, N., Mota, B. C., Stead, L., Palmer, E. O. C., Lombardero, L., Rodríguez-Puertas, R., de Paola, V., Barnes, S. J., & Sastre, M. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02117-y · Cited by 65
Calsolaro, V., Matthews, P. M., Donat, C. K., Livingston, N. R., Femminella, G. D., Guedes, S. D. S., Myers, J., Fan, Z., Tyacke, R. J., Venkataraman, A. V., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01193-z · Cited by 63
“Other studies have also shown that GFAP co-localises with Aβ [53–55], and that GFAP can attenuate Aβ load [4, 56], suggesting astrocyte reactivity can occur in response to Aβ pathology.”
BackgroundThe Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review
Hulshof, L. A., van Nuijs, D., Hol, E. M., & Middeldorp, J. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.899251 · Cited by 66
Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke
Andrade, M. F., Wang, N., Bechberger, J. F., Bock, M. D., Lampe, P. D., Leybaert, L., & Naus, C. C. G. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20171452 · Cited by 64
“Several lines of evidence show that reactive astrocytes are involved in neuronal survival mechanisms in stroke and neurodegeneration (Li et al., 2008; Kraft et al., 2013; Kamphuis et al., 2015).”
BackgroundSaha, P., Sarkar, S., Paidi, R. K., & Biswas, S. C. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.03.014 · Cited by 63
The impact of astrocytic NF-κB on healthy and Alzheimer’s disease brains
Huat, T. J., Camats‐Perna, J., Newcombe, E. A., Onraet, T., Campbell, D., Sucic, J. T., Martini, A. C., Forner, S., Mirzaei, M., Poon, W. W., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-65248-1 · Cited by 64
“…models increased monomeric Aβ production and reduced degradation of Aβ, heightened expression of pro-inflammatory cytokines, decreased expression of synaptic markers, and exacerbated cognitive deficits 98–100 , supporting the fundamental role of these cells in counterbalancing the disease process.”
Hascup, E. R., Broderick, S. O., Russell, M. K., Fang, Y., Bartke, A., Boger, H. A., & Hascup, K. N. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14634 · Cited by 62
Nirzhor, S. S. R., Khan, R. I., & Neelotpol, S. (2018) · Biomolecules · doi:10.3390/biom8030093 · Cited by 57
“Astrocytes may upregulate the protein known as glial fibrillary acidic protein (GFAP), which regulates immune response in the CNS, especially in neurodegeneration or traumatic brain injury [76,77] Studies in APP/PS1 mice have shown that the deletion of GFAP, which inhibits astrogliosis, showed a marked increase in Aβ…”
BackgroundRadulovic, M., Yoon, H., Wu, J., Mustafa, K., & Scarisbrick, I. A. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.04.010 · Cited by 59
“…being documented in SCI (Faulkner et al., 2004; Herrmann et al., 2008), and other disorders including stroke (Li et al., 2008; Liu et al., 2014), EAE (Liedtke et al., 1998; Voskuhl et al., 2009; Toft-Hansen et al., 2011), Alzheimers (Kraft et al., 2013) and Parkinsons (Shao et al., 2013).”
InfluentialSelf-citationDashkoff, J., Lerner, P., Truong, N., Klickstein, J. A., Fan, Z., Mu, D., Maguire, C. A., Hyman, B. T., & Hudry, E. (2016) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2016.81 · Cited by 57
Exercise-Induced Modulation of Neuroinflammation in Models of Alzheimer’s Disease
Kelly, Á. M. (2018) · Brain Plasticity · doi:10.3233/bpl-180074 · Cited by 55
“Astrocytes are the most populous cells in the CNS, where they provide structural and functional support to neurons, form part of the blood brain barrier (BBB) and participate in synaptic formation [172].”
BackgroundInfluentialSkalli, O., Wilhelmsson, U., Örndahl, C., Fekete, B., Malmgren, K., Rydenhag, B., & Pekny, M. (2013) · Human Pathology · doi:10.1016/j.humpath.2013.03.013 · Cited by 54
“c P values were obtained by analyzing contingency tables with the 2-tailed with acute or chronic cellular stress of diverse kind, for example, in acute neurotrauma [28,30], focal brain ischemia [31], retinal injury [32], Batten disease [33], or Alzheimer disease [34].”
MethodSelf-citationPharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis
Livne‐Bar, I., Lam, S., Chan, D. W.-H., Guo, X., Askar, I., Nahirny, A., Flanagan, J. G., & Sivak, J. M. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.277 · Cited by 56
“outgrowth and regeneration in developing neurons and models of CNS injury, yet result in developmental defects to inner retinal function(13) and increased damage in models of Alzheimer’s disease.(14) Genetically, GFAP gain of function”
BackgroundHIF‐1α Mediates Isoflurane‐Induced Vascular Protection in Subarachnoid Hemorrhage
Milner, E., Johnson, A. W., Nelson, J. W., Harries, M. D., Gidday, J. M., Han, B. H., & Zipfel, G. J. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.170 · Cited by 52
“qPCR was performed as described.(32) Briefly, following transcardial perfusion with heparinized PBS, cortex was rapidly”
MethodCalcium Signalling Toolkits in Astrocytes and Spatio-Temporal Progression of Alzheimer's Disease
Lim, D., Rodríguez-Arellano, J. J., Parpura, V., Zorec, R., Zeidán‐Chuliá, F., Genazzani, A. A., & Verkhratsky, A. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666151116130104 · Cited by 52
The role of Locus Coeruleus in neuroinflammation occurring in Alzheimer’s disease
Giorgi, F. S., Saccaro, L. F., Galgani, A., Busceti, C. L., Biagioni, F., Frati, A., & Fornai, F. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.08.007 · Cited by 53
Good, bad, and neglectful: Astrocyte changes in neurodegenerative disease
Jiwaji, Z., & Hardingham, G. E. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.02.020 · Cited by 53
Synergistic Actions of Microglia and Astrocytes in the Progression of Alzheimer's Disease
Bouvier, D. S., & Murai, K. K. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-143156 · Cited by 52
“Consistent with this concept, genetic deletion of the intermediate filament proteins, GFAP and vimentin, known to be upregulatedinreactiveastrocytes,inA PP/PS1miceworsened A plaque load and neuritic dystrophy [137].”
BackgroundOksanen, M., Hyötyläinen, I., Trontti, K., Rõlova, T., Wojciechowski, S., Koskuvi, M., Viitanen, M. H., Levonen, A., Hovatta, I., Roybon, L., et al. (2019) · Glia · doi:10.1002/glia.23741 · Cited by 49
“Astrocytes have been shown to contribute to both Aβ production and clearance (Kraft et al., 2013; Ries & Sastre, 2016) and also be significant targets themselves for Aβ toxicity.”
BackgroundIn vivo spatiotemporal dynamics of astrocyte reactivity following neural electrode implantation
Savya, S. P., Li, F., Lam, S., Wellman, S. M., Stieger, K. C., Chen, K., Eles, J. R., & Kozai, T. D. Y. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121784 · Cited by 46
Enhanced delivery of a low dose of aducanumab via FUS in 5×FAD mice, an AD model
Kong, C., Yang, E.-J., Shin, J., Park, J., Kim, S., Park, S., Chang, W. S., Lee, C., Kim, H.-J., Kim, H.-S., et al. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00333-x · Cited by 52
“Several studies have reported the role of impaired function of GABAA receptors by modulating neuronal activity in AD [50, 51].”
BackgroundThe contribution of astrocytes to Alzheimer's disease
Birch, A. M. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140171 · Cited by 51
Circadian regulation of astrocyte function: implications for Alzheimer’s disease
McKee, C. A., Lananna, B. V., & Musiek, E. S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03314-y · Cited by 49
Blossom, V., Ullal, S. D., D’Souza, M. M., Ranade, A. V., Kumar, N. A., & Rai, R. (2025) · 3 Biotech · doi:10.1007/s13205-025-04468-2 · Cited by 57
“On the contrary, studies in the APP/PS1 mouse model of AD showed that the decrease of GFAP and vimentin is directly proportional to the astrocytic reaction and inversely proportional to that of the Aβ plaque load (Kraft et al 2013).”
Minocycline Reduces Spontaneous Hemorrhage in Mouse Models of Cerebral Amyloid Angiopathy
Yan, P., Zhu, A., Liao, F., Xiao, Q.-L., Kraft, A. W., Gonzales, E., Perez, R., Greenberg, S., Holtzman, D., & Lee, J.-M. (2015) · Stroke · doi:10.1161/strokeaha.115.008582 · Cited by 35
“Area stained with the amyloid dye was quantified and expressed as mean fraction of section area from each mouse.(21) Groups were compared using Student t test or Mann–Whitney rank-sum test.”
MethodSelf-citationBerg, A., Zelano, J., Pekna, M., Wilhelmsson, U., Pekny, M., & Cullheim, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079395 · Cited by 47
“faster progression of neurodegenerative diseases, such as Alzheimer’s disease [13] or Batten disease [14].”
BackgroundSelf-citationHeterogeneity of Notch signaling in astrocytes and the effects of GFAP and vimentin deficiency
Lebkuechner, I., Wilhelmsson, U., Möllerström, E., Pekna, M., & Pekny, M. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13213 · Cited by 45
Self-citationPeroxiredoxin 6 mediates protective function of astrocytes in Aβ proteostasis
Pankiewicz, J. E., Diaz, J. R., Martá-Ariza, M., Lizińczyk, A. M., Franco, L. A., & Sadowski, M. J. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00401-8 · Cited by 47
“Deletion of Gfap and vimentin genes encoding intermediate filaments of astrocytic cytoskeleton was shown to impair migration of astrocytes toward Aβ plaques, which resulted in accelerated plaque pathogenesis and enhanced neuritic degeneration in AD Tg mice [62].”
BackgroundDysfunction of the neurovascular unit in diabetes-related neurodegeneration
Yan, C., Zhou, Y., Chen, Q., Luo, Y., Zhang, J. H., Huang, H., & Shao, A. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110656 · Cited by 47
McKee, C. A., Lee, J., Cai, Y., Saito, T., Saido, T. C., & Musiek, E. S. (2022) · Scientific Reports · doi:10.1038/s41598-022-05862-z · Cited by 47
Self-citationTopological analyses in APP/PS1 mice reveal that astrocytes do not migrate to amyloid-β plaques
Galea, E., Morrison, W., Hudry, E., Arbel‐Ornath, M., Bacskai, B. J., Gómez‐Isla, T., Stanley, E., & Hyman, B. T. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516779112 · Cited by 45
“This is based on two pieces of evidence: Astrocytes can migrate to and clear plaques ex vivo (20, 21), and impairment of astrocyte activation by deletion of genes encoding for GFAP and vimentin results in increased plaque load in APP/PS1 mice (22).”
MethodTrujillo‐Estrada, L., Jiménez, S., Castro, V. D., Torres, M., Baglietto‐Vargas, D., Moreno‐González, I., Navarro, V., Sanchez-Varo, R. M., Sánchez‐Mejías, E., Dávila, J. C., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-73 · Cited by 44
“It has been suggested that astrocytes could play a prominent role by limiting the plaque growth and the plaque-associated dystrophy formation [35,36].”
BackgroundHou, Y., Wang, Y., Zhao, J., Li, X., Cui, J., Ding, J., Wang, Y., Zeng, X., Ling, Y., Shen, X., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111215 · Cited by 43
Self-citationYang, J., Zhang, R., Shi, C., Mao, C., Yang, Z.-H., Suo, Z., Torp, R., & Xu, Y. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160957 · Cited by 42
“In contrast, the study by Kraft demonstrated that deletion of GFAP and vimentin accelerates plaque pathogenesis in APP/PS1 mice [36].”
A role for ErbB signaling in the induction of reactive astrogliosis
Chen, J., He, W., Hu, X., Shen, Y., Cao, J., Wei, Z., Luan, Y., He, L., Jiang, F., & Tao, Y. (2017) · Cell Discovery · doi:10.1038/celldisc.2017.44 · Cited by 42
Self-citationMarongiu, R. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00242 · Cited by 47
“…that causes the reduction of Aβ removal from the brain, and activates chronic inflammation, factors that accelerate the neuropathology and cognitive impairment in AD (Zlokovic, 2011; Carnevale et al., 2012; Shah et al., 2012; Attems and Jellinger, 2014; Kruyer et al., 2015; Faraco et al., 2016).”
BackgroundBouvier, D. S., Fixemer, S., Heurtaux, T., Jeannelle, F., Frauenknecht, K. B. M., & Mittelbronn, M. G. A. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.814889 · Cited by 43
Regulatory T cells decrease C3-positive reactive astrocytes in Alzheimer-like pathology
Stym‐Popper, G., Matta, K., Chaigneau, T., Rupra, R., Demetriou, A., Fouquet, S., Dansokho, C., Toly‐Ndour, C., & Dorothée, G. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02702-3 · Cited by 45
“Whereas some previous evidence suggested a potential beneficial impact of reactive astrocytes in Alzheimer’s disease [12], recent studies support an enrichment of C3+ potentially pro-inflammatory neurotoxic A1-like reactive astrocytes in a mouse model of AD-like amyloid pathology [13] and in post-mortem tissues from p…”
ResultAstrocytes: The Stars in Neurodegeneration?
Dittlau, K. S., & Freude, K. (2024) · Biomolecules · doi:10.3390/biom14030289 · Cited by 39
“In AD, amyloid plaque deposition increased in an APPswe/PS1 E9 transgenic mouse model when astrocyte reactivity was reduced through glial fibrillary acid protein (GFAP)/Vimentin double knockout [36].”
Tsoy, A., Saliev, T. M., Abzhanova, E., Turgambayeva, A., Kaiyrlykyzy, A., Akishev, M., Saparbayev, S. S., Umbayev, B. A., & Askarova, S. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.03.058 · Cited by 39
Ghoneim, F. M., Khalaf, H. A., Elsamanoudy, A. Z., El‐khair, S. M. A., Helaly, A. M. N., Mahmoud, E.-H. M., & Elshafey, S. H. (2015) · PubMed Central · Cited by 37
Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer’s Disease
Lee, E., & Chang, Y. (2025) · Cells · doi:10.3390/cells14030168 · Cited by 39
“This provides strong evidence that astrocytes closely interact with amyloid plaques [29,85].”
van Gijsel‐Bonnello, M., Baranger, K., Benech, P., Rivera, S., Khrestchatisky, M., Reggi, M. L. D., & Gharib, B. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194586 · Cited by 35
Synemin is expressed in reactive astrocytes and Rosenthal fibers in Alexander disease
Pekny, T., Faiz, M., Wilhelmsson, U., Curtis, M. A., Matěj, R., Skalli, O., & Pekny, M. (2013) · Apmis · doi:10.1111/apm.12088 · Cited by 39
“implicated (20, 21), but remains incompletely understood.”
Self-citationGarcía‐León, J. A., Cáceres-Palomo, L., Sánchez‐Mejías, E., Mejias‐Ortega, M., Nuñez‐Diaz, C., Fernandez-Valenzuela, J. J., Sanchez-Varo, R. M., Dávila, J. C., Vitórica, J., & Gutiérrez, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186867 · Cited by 35
“In relation with Aβ plaques, reactive astrocytes limit the progression of Aβ plaques [97] likely through direct phagocytosis and degradation of Aβ species [98].”
BackgroundAstrocyte subtype-specific approach to Alzheimer's disease treatment
Sarkar, S., & Biswas, S. C. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104956 · Cited by 35
Purinergic neurone-glia signalling in cognitive-related pathologies
Illés, P., & Verkhratsky, A. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.08.005 · Cited by 34
“…however are embedded into and hence exist and perform surrounded with neuroglia, the role of which in cognition is a matter of intense debate (Blank and Prinz, 2013; Fields, 2008; Krugel et al., 2013; Pannasch and Rouach, 2013; Pereira and Furlan, 2010; Robertson, 2013; Verkhratsky et al., 2011).”
BackgroundAbbink, M. R., Kotah, J. M., Hoeijmakers, L., Mak, A., Yvon‐Durocher, G., van der Gaag, B., Lucassen, P. J., & Kőrösi, A. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01762-z · Cited by 38
Rivera-Escalera, F., Matousek, S. B., Ghosh, S., Olschowka, J. A., & O’Banion, M. K. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.018 · Cited by 34
Astrocyte Activation and the Calcineurin/NFAT Pathway in Cerebrovascular Disease
Kraner, S. D., & Norris, C. M. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00287 · Cited by 33
“…reduce amyloid pathology and improve cognitive function in mouse models of Alzhieimer’s disease, consistent with other reports that have found protective roles of activated astrocytes in neurodegenerative conditions (Okada et al., 2006; Kraft et al., 2013; Wanner et al., 2013; Tyzack et al., 2014).”
Zhang, Z., Li, D., Xu, L., & Li, H.-P. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.05.005 · Cited by 33
Targeted activation of CREB in reactive astrocytes is neuroprotective in focal acute cortical injury
Pardo, L., Schlüter, A., Valor, L. M., Barco, Á., Giralt, M., Golbano, A., Hidalgo, J., Jia, P., Zhao, Z., Jové, M., et al. (2016) · Glia · doi:10.1002/glia.22969 · Cited by 31
“…role of reactive astrocytes is still debated, the inhibition of gliosis is highly detrimental in several experimental models of brain damage including TBI (Myer et al., 2006), stab injury (Bush et al., 1999), spinal cord injury (Faulkner et al., 2004), and neurodegeneration (Kraft et al., 2013).”
BackgroundRevisiting Astrocytic Roles in Methylmercury Intoxication
Arrifano, G. D. P., Augusto‐Oliveira, M., Monteiro, J. R. S., Macchi, B. D. M., Lima, R. R., Sunol, C. E., do Nascimento, J. L. M., & Lopez, M. E. C. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02420-y · Cited by 32
Alzheimer’s Disease, Astrocytes and Kynurenines
Dézsi, L., Tuka, B., Martos, D., & Vécsei, L. (2015) · Current Alzheimer Research · doi:10.2174/156720501205150526114000 · Cited by 33
Griffith, C. M., Xie, M.-X., Qiu, W., Sharp, A. A., Ma, C., Pan, A., Yan, X., & Patrylo, P. R. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.08.034 · Cited by 33
Expression of endogenous mouse APP modulates β-amyloid deposition in hAPP-transgenic mice
Steffen, J., Krohn, M., Schwitlick, C., Brüning, T., Paarmann, K., Pietrzik, C. U., Biverstål, H., Jansone, B., Langer, O., & Pahnke, J. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0448-2 · Cited by 31
“However, astrocytes were further shown to suppress the recruitment and activation of microglia in APP/PS1 transgenic animals [19].”
Vimentin is required for normal accumulation of body fat
Wilhelmsson, U., Stillemark-Billton, P., Borén, J., & Pekny, M. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0170 · Cited by 30
“astrocyte response to neurodegeneration and facilitated progression of Alzheimer’s or Batten disease (Macauley et al., 2011; Kraft et al., 2013; Kamphuis et al., 2015).”
BackgroundSelf-citationAstrocytes: From the Physiology to the Disease
Trujillo‐Estrada, L., Gómez-Arboledas, Á., Forner, S., Martini, A. C., Gutiérrez, A., Baglietto‐Vargas, D., & LaFerla, F. M. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190830110152 · Cited by 30
Xie, Z., Yang, Q., Song, D. F., Quan, Z., & Qing, H. (2019) · Glia · doi:10.1002/glia.23693 · Cited by 31
“Likewise, astrocytes undergo degeneration and atrophy at the early stages of the pathological progression in Alzheimer's disease (AD) mouse models (Beauquis et al., 2014; Kulijewicz-Nawrot et al., 2012).”
BackgroundWunderlich, K. A., Tanimoto, N., Grosche, A., Zrenner, E., Pekny, M., Reichenbach, A., Seeliger, M. W., Pannicke, T., & Perez, M.-T. (2015) · The FASEB Journal · doi:10.1096/fj.15-272963 · Cited by 29
“This finding is in agreement with our previous results showing that GFAP2/2 mice respond as do WT mice to scrapieinduced neurodegeneration (47), whereas in Alzheimer’s (48) and Batten diseases (49), the disease progression is facilitated and the extent of neurodegeneration and neuroinflammatory response is increased o…”
ResultSelf-citationGuha, S., Paidi, R. K., Goswami, S., Saha, P., & Biswas, S. C. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.11.021 · Cited by 26
Genetic targeting of astrocytes to combat neurodegenerative disease
Kirschen, G., Kéry, R., & Chen, A. F. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.265541 · Cited by 29
“However, in transgenic mice expressing AD-associated mutant proteins amyloid precursor protein and presenilin-1, loss of GFAP and VIM lead to major increases in Aβ plaque load and neuron dysfunction, suggesting that VIM and GFAP-induced astrocyte activation and subsequent glial scarring may help to contain and limit A…”
BackgroundAnimal and Cellular Models of Alzheimer’s Disease: Progress, Promise, and Future Approaches
Trujillo‐Estrada, L., Sánchez‐Mejías, E., Sanchez-Varo, R. M., García‐León, J. A., Nuñez‐Diaz, C., Dávila, J. C., Vitórica, J., LaFerla, F. M., Moreno‐González, I., Gutiérrez, A., et al. (2021) · The Neuroscientist · doi:10.1177/10738584211001753 · Cited by 30
Astrocyte adaptation in Alzheimer’s disease: a focus on astrocytic P2X7R
Beltran-Lobo, P., Reid, M. J., Jiménez-Sánchez, M., Verkhratsky, A., Perez‐Nievas, B. G., & Noble, W. J. (2022) · Essays in Biochemistry · doi:10.1042/ebc20220079 · Cited by 30
Herzer, S., Hagan, C., von Gerichten, J., Dieterle, V., Munteanu, B., Sandhoff, R., Hopf, C., & Nordström, V. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00206 · Cited by 27
Astrocyte-mediated metaplasticity in the hippocampus: Help or hindrance?
Jones, O. D. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.08.035 · Cited by 30
Jiang, Z., Wang, J., Qin, Y., Liu, S., Luo, B., Bai, F., Wei, H., Zhang, S., Wei, J., Ding, G., et al. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01392-0 · Cited by 32
“Such astrocyte activation can be either harmful due to the loss of neurotrophic effects and the overproduction of proinflammatory molecules or helpful because of the attenuation of Aβ plaque growth and reduction in dystrophic neurites [56–59].”
BackgroundWeinberg, R. P., Koledova, V. V., Schneider, K., Sambandan, T. G., Grayson, A. R., Zeidman, G., Artamonova, A., Sambanthamurthi, R., Fairus, S., Sinskey, A. J., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-34763-3 · Cited by 25
PPARα Between Aspirin and Plaque Clearance
Chandra, S., Roy, A., Patel, D. R., & Pahan, K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190586 · Cited by 23
“…study demonstrated that attenuating astrocytic activation by deletion of genes encoding intermediate filament proteins, glial fibrillary acidic protein (GFAP) and vimentin, accelerates the amy-loidplaquepathogenesissuggestinganimportantrole of astrocyte activation in preventing AD pathogenesis [28].”
Biological agents and the aging brain: glial inflammation and neurotoxic signaling
Latham, A. S., Moreno, J. A., & Geer, C. E. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1244149 · Cited by 27
“Inhibiting the ability of astrocytes to activate, but not completely eliminating them, also exacerbates amyloid β deposition (Kraft et al., 2013).”
BackgroundPathologic and clinical correlates of region-specific brain GFAP in Alzheimer’s disease
Phillips, J. M., Winfree, R. L., Seto, M., Schneider, J. A., Bennett, D. A., Dumitrescu, L. C., & Hohman, T. J. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02828-5 · Cited by 25
Jiao, M., Wang, C., Tang, X., Dai, C., Zhang, N., Fan, A., Qian, Z., Liu, S., Zhang, F. S., Li, B., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.04.028 · Cited by 25
Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes
de Pablo, Y., Marášek, P., Pozo-Rodrigálvarez, A., Wilhelmsson, U., Inagaki, M., Pekna, M., & Pekny, M. (2019) · Cells · doi:10.3390/cells8091016 · Cited by 23
Self-citationDoroszkiewicz, J., Winkel, I., & Mroczko, B. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1579511 · Cited by 26
“In the APP/PS1 animal model of AD, the reduction of GFAP and vimentin raises the A β plaque load and decreases the astrocytic reactivity (Kraft et al., 2013).”
CIP2A-promoted astrogliosis induces AD-like synaptic degeneration and cognitive deficits
Shentu, Y.-P., Hu, W.-T., Zhang, Q., Huo, Y., Liang, J.-W., Liuyang, Z.-Y., Zhou, H., Wei, H., Ke, D., Wang, X.-C., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.11.023 · Cited by 21
“Consistently, attenuating astrocyte activation accelerates plaque deposition in APP/PS1 mice (Kraft et al., 2013).”
BackgroundThe rise of astrocytes: are they guardians or troublemakers of the brain disorder?
Kim, H. Y., Kim, S., Akaydin, A. N., Kim, S. S., Hyeon, S. J., Lee, J.-H., & Ryu, H. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01627-6 · Cited by 28
“…astrocytes constitute a subset of severe reactive astrocytes, de fi ned by their in fl ammatory induction and neurotoxic functions, whereas not all severely reactive astrocytes exhibit such detrimental effects Escartin et al. 2021 42 . enzyme (IDE) and matrix metalloproteinases (MMP-2, MMP-9) 48,49 .”
Self-citationFreude, K., Pires, C., Hyttel, P., & Hall, V. J. (2014) · Journal of Clinical Medicine · doi:10.3390/jcm3041402 · Cited by 21
“inflammatory response in the brain [137,138].”
Metadata
- Authors
- Kraft, A. W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S. C., Brown, J., Wilhelmsson, U., Restivo, J. L., Cirrito, J. R., Holtzman, D. M., Kim, J., Pekny, M., & Lee, J.
- Affiliations
- Washington University in St. Louis (US)
- University of Gothenburg (SE)
- Corresponding author
- Lee, Jin‐Moo
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2012-10-04
- Volume
- 27
- Issue
- 1
- Pages
- 187-198
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC3528309
- OpenAlex
- W2164490896
- Semantic Scholar
- 459fcf0772019eda0ac89ec7c2f7f0ff9d4dbe73
- Cited by
- 324
- References
- 69
- Citations by year
- 2026: 20 · 2025: 23 · 2024: 24 · 2023: 17 · 2022: 21 · 2021: 25 · 2020: 25 · 2019: 30 · 2018: 27 · 2017: 21 · 2016: 19 · 2015: 30 · 2014: 28 · 2013: 14
- FWCI
- 13.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institutes of Health (R01 NS48283, R01 NS67905, P01 NS32636, R37 AG13956, P30NS69329)
- Medicinska Forskningsrådet (11548)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- astrocyte activation, amyloid plaques, Alzheimer's disease, amyloid-beta, APP/PS1 mice, glial fibrillary acidic protein, vimentin, intermediate filaments, dystrophic neurites, astrocyte morphology, plaque progression
- MeSH terms
- Animals, Astrocytes, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Blotting, Western, Amyloid beta-Protein Precursor, Mice, Presenilin-1, Real-Time Polymerase Chain Reaction
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