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Extracellular Vesicles From 3xTg-AD Mouse and Alzheimer's Disease Patient Astrocytes Impair Neuroglial and Vascular Components
González-Molina LA, Villar-Vesga J, Henao-Restrepo J, Villegas A, Lopera F, Cardona-Gómez GP, Posada-Duque R.. Frontiers in aging neuroscience, 2021-02-19
Topic: Brain proteins, microglia and lab models
Astrocytes are specialized glial cells that are essential components of the neurovascular unit (NVU) and are involved in neurodevelopment, brain maintenance and repair, and neurodegeneration. Astrocytes mediate these processes by releasing cellular mediators such as extracellular vesicles (EVs). EVs are vehicles of cell-cell communication and have been proposed as mediators of damage in AD. However, the transcellular mechanism by which Alzheimer disease (AD) astrocytes impair the function of NVU components is poorly understood. Therefore, we evaluated the effects of adult PS1-KI and 3xTg-AD astrocyte conditioned media (CM) and EVs on NVU components (neuroglia and endothelium) in vitro . Additionally, SAD and FAD astrocyte-derived EVs (A-EVs) were characterized, and we evaluated their effects on NVU in cocultured cells in vitro and on intrahippocampal CA1 cells in vivo . Surprisingly, cultured 3xTg-AD astrocytes showed increased glial fibrillary acidic protein (GFAP) reactivity compared to PS1-KI astrocytes, which denotes astrocytic hyperreactivity. CM from adult mice 3xTg-AD astrocytes increased cell-cell gaps between endothelial cells, filopodia-like dendritic protrusions in neurons and neuronal and endothelial cell death. 3xTg-AD A-EVs induced neurotoxicity and increased astrocyte GFAP reactivity. Cultured human postmortem astrocytes from AD patients also increased GFAP reactivity and EVs release. No differences in the size or number of A-EVs were detected between AD and control samples; however, both SAD and FAD A-EVs showed increased expression of the surface marker aquaporin 4. A-EVs induced cytotoxicity and astrocyte hyperactivation: specifically, FAD A-EVs induced neuroglial cytotoxicity and increased gaps between the endothelium, while SAD A-EVs mainly altered the endothelium. Similarly, both AD A-EVs increased astrocyte GS reactivity and vascular deterioration in vivo . We associated this finding with perivascular reactive astrocytes and vascular deterioration in the human AD brain. In summary, these results suggest that AD A-EVs impair neuroglial and vascular components.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
González-Molina, L. A., Villar-Vesga, J., Henao-Restrepo, J., Villegas, A., Lopera, F., Cardona-Gómez, G. P., et al. (2021). Extracellular Vesicles From 3xTg-AD Mouse and Alzheimer's Disease Patient Astrocytes Impair Neuroglial and Vascular Components. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2021.593927
Vancouver
González-Molina LA, Villar-Vesga J, Henao-Restrepo J, Villegas A, Lopera F, Cardona-Gómez GP, et al. Extracellular Vesicles From 3xTg-AD Mouse and Alzheimer's Disease Patient Astrocytes Impair Neuroglial and Vascular Components. Frontiers in aging neuroscience. 2021. doi:10.3389/fnagi.2021.593927. PMID: 33679370.
BibTeX
@article{gonzalezmolina2021-33679370,
author = {González-Molina, L. A. and Villar-Vesga, J. and Henao-Restrepo, J. and Villegas, A. and Lopera, F. and Cardona-Gómez, G. P. and Posada-Duque, R.},
title = {{Extracellular Vesicles From 3xTg-AD Mouse and Alzheimer's Disease Patient Astrocytes Impair Neuroglial and Vascular Components}},
journal = {Frontiers in aging neuroscience},
year = {2021},
doi = {10.3389/fnagi.2021.593927},
pmid = {33679370},
url = {https://doi.org/10.3389/fnagi.2021.593927}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Surprisingly, cultured 3xTg-AD astrocytes showed increased glial fibrillary acidic protein (GFAP) reactivity compared to PS1-KI astrocytes, which denotes astrocytic hyperreactivity.
- In summary, these results suggest that AD A-EVs impair neuroglial and vascular components.
Why it matters
Extracellular vesicles from Alzheimer disease mouse and patient astrocytes impaired neuroglial and vascular components in laboratory and animal experiments. This suggests a mechanism by which astrocytes may contribute to damage, but it is early laboratory work and no treatment was tested in people.
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Study details
- Evidence strengthLow
How this study scored 37/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in aging neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Aging Neuroscience: journal h-index 174 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “3xtg”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 37 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Rafael Posada‐Duque: h-index 14 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Universidad de Antioquia: institution h-index 298 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33679370) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
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