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.
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- 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.
- 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.
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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Astrocyte activation and reactive gliosis
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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 201–300 of 324
Ma, K., Lv, J., Yang, W., Chang, K.-W., Hu, X., Shi, L., Zhai, W.-Y., Zong, H.-F., & Qian, Y. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.11.006 · Cited by 21
Self-citationPrinciples of Astrogliopathology
Verkhratsky, A., Li, B., Scuderi, C., & Parpura, V. (2021) · Advances in Neurobiology · doi:10.1007/978-3-030-77375-5_3 · Cited by 21
“Furthermore, inhibition of astroglial reactivity results in higher accumulation of β-amyloid and reduced microglial association with senile plaques in the animal model of Alzheimer’s disease (AD); all these changes seem to exacerbate AD-type pathology (Kraft et al. 2013).”
BackgroundNeuronal Injury and Glial Changes Are Hallmarks of Open Field Blast Exposure in Swine Frontal Lobe
Kallakuri, S., Desai, A., Feng, K., Tummala, S., Saif, T., Chen, C.-Y., Zhang, L.-Y., Cavanaugh, J., & King, A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169239 · Cited by 20
Astrocytes: Initiators of and Responders to Inflammation
Soung, A., & Klein, R. S. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.89760 · Cited by 19
Mens sana in corpore sano: lifestyle changes modify astrocytes to contain Alzheimer’s disease
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“Inhibition of astroglial reactivity by genetic deletion of intermediate filaments glial fibrillary acidic protein (GFAP) and vimentin exacerbate β-amyloid pathology (Kraft et al., 2013), indicating defensive potential of reactive astroglia in AD.”
BackgroundDong, X., & Qu, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.877872 · Cited by 18
Ceyzériat, K., Badina, A. M., Petrelli, F., Montessuit, S., Nicolaides, A., Millet, P., Savioz, A., Martinou, J.-C., & Tournier, B. B. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106623 · Cited by 18
“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).”
BackgroundHypothyroidism affects astrocyte and microglial morphology in type 2 diabetes
Nam, S., Kim, Y. N., Yoo, D., Yi, S.-S., Choi, J.-H., Hwang, I., Seong, J., & Yoon, Y. (2013) · Neural Regeneration Research · doi:10.3969/j.issn.1673-5374.2013.26.007 · Cited by 19
“Additionally, the astrogliosis is considered as neuroprotective actions against neuronal damages [28-29] .”
BackgroundThe role of ADAM10 in astrocytes: Implications for Alzheimer’s disease
Elsworthy, R. J., Hill, E. J., Dunleavy, C., & Aldred, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1056507 · Cited by 17
“Inhibiting astrogliosis can accelerate Aβ accumulation in AD mice (Kraft et al., 2013) indicating a protective role for astrocyte reactivity.”
BackgroundSinghaarachchi, P. H., Antal, P., Calon, F., Culmsee, C., Delpech, J.-C., Feldotto, M., Geertsema, J., Hoeksema, E. E., Kőrösi, A., Layé, S., et al. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105724 · Cited by 20
“In APP/PS1 mice, inactivation of prominent indicators of reactive astrocytes like glial fibrillary acidic protein (GFAP) and vimentin (Kamphuis et al., 2015) leads to an increased A β deposition, suggesting that astrocytic activation limits plaque expansion (Kraft et al., 2013).”
BackgroundVillareal, J. A. B., Bathe, T., Hery, G. P., Phillips, J. L., Tsering, W., & Prokop, S. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03196-3 · Cited by 17
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“On the other hand, astrocytes actively participate in limiting plaque growth in APP/PS1 mice [39].”
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Self-citationThe Role of Astrocytes in Synaptic Dysfunction and Memory Deficits in Alzheimer’s Disease
de León-López, C. A. M., Navarro‐Lobato, I., & Khan, Z. U. (2025) · Biomolecules · doi:10.3390/biom15070910 · Cited by 19
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Aspects of the immune system that impact brain function
Bondy, S. C. (2020) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2020.577167 · Cited by 14
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“The relationship between reactive microglia, reactive astrocytes, and plaques is still not elucidated [13, 26, 29, 37, 38, 42, 44, 48, 49], and it remains unclear whether the presence of inflammation in different brain regions is beneficial or is just a consequence, and so, it is not altering the progression of the di…”
BackgroundMethodJOTROL, a Novel Formulation of Resveratrol, Shows Beneficial Effects in the 3xTg-AD Mouse Model1
Dennison, J. L., Volmar, C., Modarresi, F., Ke, D., Wang, J., Gravel, E., Vignini-Hammond, S., Li, Z., Timmons, J. A., Lohse, I., et al. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215370 · Cited by 13
“…in the 3xTg-AD mice are not fully understood; however, genetic knockout of Gfap in APP/PS1 mice have resulted in increased levels of A (cid:2) plaque deposition and changes in inflamma-tory response, implying that reactive astrocytes may be needed to mitigate AD-like pathogenesis [44, 45].”
Liu, H.-J., Wang, M., Wang, Y., Shi, S., Hu, X., Zhang, D.-B., Fan, D., Mintzer, J., & Xu, P. (2025) · Cell Biomaterials · doi:10.1016/j.celbio.2025.100158 · Cited by 13
Self-citationRefining the interactions between microglia and astrocytes in Alzheimer’s disease pathology
Chen, J., Xu, S., Wang, L., Liu, X., Liu, G., Tan, Q., Li, W., Zhang, S., & Du, Y. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.03.033 · Cited by 17
Astrocyte Reactivity in Alzheimer’s Disease: Therapeutic Opportunities to Promote Repair
Mirzaei, N., Davis, N., Chau, T. W., & Sastre, M. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666211029164106 · Cited by 12
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“The astroglial juxtaposition is hypothesized to control Aβ plaque deposition [69] through a variety of clearance mechanisms [70].”
NR3C1-mediated epigenetic regulation suppresses astrocytic immune responses in mice
Park, S., Park, H., Byun, Y. G., Wei, X., Eom, J., Joo, J., Lee, A., Diao, Y., Chung, W., & Jung, I. (2025) · Nature Communications · doi:10.1038/s41467-025-64088-5 · Cited by 13
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Efficacy of exercise rehabilitation for managing patients with Alzheimer’s disease
Li, D., Jia, J., Zeng, H., Zhong, X., Chen, H., & Yi, C. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.391308 · Cited by 15
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“On the other hand, inhibition of astrocyte reactivity causes acceleration of A β plaque pathology in mice (Kraft et al., 2013).”
Immune cells in Alzheimer’s disease: insights into pathogenesis and potential therapeutic targets
Fu, X., Cai, H., Quan, S., Ren, Z., Xu, Y., & Jia, L. (2024) · Medical Review · doi:10.1515/mr-2024-0064 · Cited by 10
“However, with the accumulation of A β , the function of reactive astrocytes may change from a protective phenotype, capable of uptake and degradation of A β , to a harmful phenotype, possibly capable of uptake but ine ff ective in its degradation [102].”
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“In the APP/PS1 AD mice model, a positive correlation was found between gliosis and A β -plaque growth by in vivo multiphoton microscopy [36], whereas this correlation was negative in ex vivo investigations after attenuation of astrocyte reactivity [37].”
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Significant enhanced expressions of aquaporin-1, -4 and -9 in the brains of various prion diseases
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The Implication of Glial Metabotropic Glutamate Receptors in Alzheimer’s Disease
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“Although the precise mechanisms remain unclear, Aβ-induced neuro-inflammation, mediated by activated microglia [12, 13] and astrocytes [14–16] is thought to exacerbate tau pathology.”
Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease
Qin, H., Zhou, L., Haque, F. T., Martín-Jiménez, C., Trang, A., Benveniste, E. N., & Wang, Q. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.16002 · Cited by 10
“…astrocytes or overall attenuation of astrocyte reactivity significantly exacerbates A β pathology and memory deficits (Katsouri et al., 2020 ; Kraft et al., 2013 ), underscoring the complexity of the involvement of reactive astrocytes in AD and the challenge of targeting astrocytes for AD…”
Deletion of MyD88 in astrocytes prevents β‐amyloid‐induced neuropathology in mice
Huat, T. J., Onraet, T., Camats‐Perna, J., Newcombe, E. A., Ngo, K. C., Sue, A. N., Mirzaei, M., LaFerla, F. M., & Medeiros, R. (2022) · Glia · doi:10.1002/glia.24285 · Cited by 8
“and exacerbated cognitive deficits (Davis et al., 2021; Katsouri et al., 2020; Kraft et al., 2013).”
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“In addition, the role of GFAP in neuronal regeneration, scar formation and amyloid load assimilation remains unclear (31,32).”
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Self-citationGADD45G operates as a pathological sensor orchestrating reactive gliosis and neurodegeneration
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Astrocyte–Neuron Interactions in Alzheimer’s Disease
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Neuroglia in neurodegeneration: Alzheimer, Parkinson, and Huntington disease
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“Attenuation of reactive astrocytes increased the Ab load in AD model mice.(97) Therefore, direct programming of microglia and astrocytes into functional neurons in AD might not be effective for the prevention of disease progression.”
BackgroundChen, Y., Mancuso, J. J., Zhao, Z., Li, X., Cheng, J., Román, G. C., & Wong, S. T. C. (2013) · Journal of Biomedical Optics · doi:10.1117/1.jbo.18.12.126012 · Cited by 7
“Recently, astrocyte activation has been proposed as a potential means to increase local CBF(13) and as a novel therapeutic target for neurodegeneration, such as AD.(7) It is well known”
BackgroundInfluentialDeciphering T Cell Dynamics in Alzheimer's Disease Pathogenesis: Insights and Implications
Yang, Q., Qiu, Y., Ni, J., Li, H., & Qing, H. (2025) · Current Neuropharmacology · doi:10.2174/011570159x350611250303044527 · Cited by 7
“Some evidence suggests that reactive astrocytes can limit the growth of amyloid plaques and reduce associated neuronal damage [68].”
Alcohol dependence-induced astrocyte immune activation in the nucleus accumbens
Hashimoto, J. G., Mangieri, R. A., Roberts, A. J., Lime, T., Davis, B. A., Carbone, L., Roberto, M., & Guizzetti, M. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107171 · Cited by 7
“Reactive astrocytes provide adaptive responses to initial brain insults and the attenuation of astrocyte reactivity can exacerbate tissue injury and worsen diseases’ outcomes (Bush et al., 1999; Faulkner et al., 2004; Kraft et al., 2013; Liu et al., 2014).”
Beclin 1 regulates astrocyte phagocytosis and phagosomal recruitment of retromer
Silva, E. G. L., Delgadillo, Y., White, R., & Lucin, K. M. (2023) · Tissue and Cell · doi:10.1016/j.tice.2023.102100 · Cited by 6
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“In amyloid mouse models, inhibition of reactive astrogliosis increases Aβ 42 plaque burden [69], whereas shifting microglia to an interferon-responsive state boosts ApoE expression, phagocytosis, containment of plaques, and lessens damage to nearby neurons and synapses [70].”
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“In support of this, in vivo and ex vivo animal studies have shown that reduced astrocyte function is associated with reduced Aβ clearance and increased plaque load [65, 66].”
Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer’s disease progression
Lana, D., Ugolini, F., Iovino, L., Attorre, S., & Giovannini, M. G. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1512985 · Cited by 6
Role of astrocytes in Alzheimer's disease pathogenesis and the impact of exercise-induced remodeling
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p35 Hemizygous Deletion in 5xFAD Mice Increases Aβ Plaque Load in Males but Not in Females
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Transcriptome and Translatome Regulation of Pathogenesis in Alzheimer’s Disease Model Mice
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BMAL1-GPX3 axis in the choroid plexus mitigates Aβ pathology in an amyloid mouse model
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“Astrocytic morphological complexity is positively correlated with their ability to respond to plaques [32, 33].”
Curing the brain: in search for new astrocyte-specific therapies
Verkhratsky, A., Lee, C. J., Chun, H., Göritz, C., Harkany, T., Lee, J., Lee, S., Lindskog, M., Koh, W., Mulder, J., et al. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01712-4 · Cited by 8
“These reactive glial barriers are, arguably, protective against β -amyloid toxicity 195,196 , whereas suppression of reactive astrogliosis exacerbates pathology in AD animal models 197 .”
Self-citationLactate metabolism links reactive microglia, amyloid pathology, and Aβ dynamics
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“5B) [59], we also analyzed GFAP + immunoreactivity.”
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“It has been demonstrated that neuropathic pain induced by chronic constriction injury (CCI) leads to an increase in total calcium in tissues and the presence of free radicals (Kraft et al. 2013).”
The involvement of neuronal chloride transporter deficiencies in epilepsy
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The Double Face of Microglia in the Brain
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“Numerous research efforts have associated astrocyte activation with an increased plaque burden [112–114], while others have linked astrocyte activation to a decrease in plaque burden [115,116].”
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“Additionally, the knockout of Gfap and Vim in a mouse model of Alzheimer's disease (AD) resulted in increased amyloid plaque deposition [7].”
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“, 2011) while in the APP/PS1dE9 AD mice, it increased amyloid β load and the number of dystrophic neurites in the hippocampus (Kraft et al., 2013).”
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HISTOLOGICAL AND BEHAVIORAL CONSEQUENCES OF REPEATED MILD TRAUMATIC BRAIN INJURY IN MICE
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“However, these findings directly conflict with another study showing that blocking astrocyte activation lead to increased plaque load that they propose may be due to decreased clearance since Aβ production was unchanged (Kraft et al., 2013).”
ResultTargeting Astrocytes With Viral Gene Therapy for Alzheimer’s Disease
Rosenthal, Z. P., Kraft, A. W., Czerniewski, L. R., & Lee, J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809813-4.00005-3
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“…reactive astrocytes can contribute to neurotoxicity while also supporting Aβ-clearance through endo-lysosomal degradation (Boisvert et al., 2018; Funato et al., 1998; Jones et al., 2013; Kamphuis et al., 2015; Kraft et al., 2012; Nagele et al., 2003; Söllvander et al., 2016; Xiao et al., 2014).”
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Cerebrovascular Dysfunction and Degeneration in Alzheimer’s Disease Pathophysiology
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Henniges, P. (2023) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9694
Verkhratsky, A., & Butt, A. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821565-4.00005-5
Glial Cell Biology and Their Multifaceted Functions in Alzheimer's Disease
Laadraoui, J., Kabdy, H., Azraida, H., Aimrane, A., & Smimih, K. (2023) · Advances in bioinformatics and biomedical engineering book series · doi:10.4018/978-1-6684-9675-6.ch015
Saido, T. C. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-28979-8.00023-1
Mutations in GFAP Alter Early Lineage Commitment of Organoids
Dykstra, W., Matusova, Z., Battaglia, R. A., Abaffy, P., Goya‐Iglesias, N., Pérez‐Sala, D., Ahlenius, H., Kubista, M., Pasterkamp, R. J., Li, L., et al. (2025) · Glia · doi:10.1002/glia.70049
“…such as neurotrauma (Cho et al. 2005; Grosche et al. 2013; Lundkvist et al. 2004; Wilhelmsson et al. 2004), CNS ischemia (Aswendt et al. 2022; Järlestedt et al. 2010; Li et al. 2008; Verardo et al. 2008) or neurodegenerative diseases (Kamphuis et al. 2015; Kraft et al. 2013; Macauley et al. 2011).”
Self-citationAstrocytes: Multiscale Molecular Targets for Glial Engineering and Interfaces
Konstantoulaki, A., Fabbri, R., Conte, G., Lazzarini, C., & Benfenati, V. (2025) · Springer eBooks · doi:10.1007/978-3-031-94215-0_1
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-17, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-17 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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