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GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease
Kamphuis W, Mamber C, Moeton M, Kooijman L, Sluijs JA, Jansen AH, Verveer M, de Groot LR et al.. PloS one, 2012-08-13
Topic: Brain proteins, microglia and lab models
Glial fibrillary acidic protein (GFAP) is the main astrocytic intermediate filament (IF). GFAP splice isoforms show differential expression patterns in the human brain. GFAPδ is preferentially expressed by neurogenic astrocytes in the subventricular zone (SVZ), whereas GFAP(+1) is found in a subset of astrocytes throughout the brain. In addition, the expression of these isoforms in human brain material of epilepsy, Alzheimer and glioma patients has been reported. Here, for the first time, we present a comprehensive study of GFAP isoform expression in both wild-type and Alzheimer Disease (AD) mouse models. In cortex, cerebellum, and striatum of wild-type mice, transcripts for Gfap-α, Gfap-β, Gfap-γ, Gfap-δ, Gfap-κ, and a newly identified isoform Gfap-ζ, were detected. Their relative expression levels were similar in all regions studied. GFAPα showed a widespread expression whilst GFAPδ distribution was prominent in the SVZ, rostral migratory stream (RMS), neurogenic astrocytes of the subgranular zone (SGZ), and subpial astrocytes. In contrast to the human SVZ, we could not establish an unambiguous GFAPδ localization in proliferating cells of the mouse SVZ. In APPswePS1dE9 and 3xTgAD mice, plaque-associated reactive astrocytes had increased transcript levels of all detectable GFAP isoforms and low levels of a new GFAP isoform, Gfap-ΔEx7. Reactive astrocytes in AD mice showed enhanced GFAPα and GFAPδ immunolabeling, less frequently increased vimentin and nestin, but no GFAPκ or GFAP(+1) staining. In conclusion, GFAPδ protein is present in SVZ, RMS, and neurogenic astrocytes of the SGZ, but also outside neurogenic niches. Furthermore, differential GFAP isoform expression is not linked with aging or reactive gliosis. This evidence points to the conclusion that differential regulation of GFAP isoforms is not involved in the reorganization of the IF network in reactive gliosis or in neurogenesis in the mouse brain.
Key findings
- In conclusion, GFAPδ protein is present in SVZ, RMS, and neurogenic astrocytes of the SGZ, but also outside neurogenic niches.
Why it matters
This mouse study describes GFAP isoform expression in wild-type and Alzheimer disease mouse models, including increased transcript levels of GFAP isoforms in plaque-associated reactive astrocytes. It is animal work on cell biology and reports no treatment, cure or prevention.
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Study details
- Evidence strengthLow
How this study scored 53/100
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 (PloS one) |
| Journal's citation record | 4 / 4 | PLoS ONE: journal h-index 594 (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 | 1 / 5 | 2012 — within 20 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 “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 304 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.0 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 14.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 50 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Elly M. Hol: h-index 68 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22912745) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
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Read the original
- DOI: 10.1371/journal.pone.0042823
- PubMed: 22912745
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Kamphuis, W., Mamber, C., Moeton, M., Kooijman, L., Sluijs, J. A., Jansen, A. H., et al. (2012). GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease. PloS one. https://doi.org/10.1371/journal.pone.0042823
Vancouver
Kamphuis W, Mamber C, Moeton M, Kooijman L, Sluijs JA, Jansen AH, et al. GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease. PloS one. 2012. doi:10.1371/journal.pone.0042823. PMID: 22912745.
BibTeX
@article{kamphuis2012-22912745,
author = {Kamphuis, W. and Mamber, C. and Moeton, M. and Kooijman, L. and Sluijs, J. A. and Jansen, A. H. and Verveer, M. and de Groot, L. R. and others},
title = {{GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease}},
journal = {PloS one},
year = {2012},
doi = {10.1371/journal.pone.0042823},
pmid = {22912745},
url = {https://doi.org/10.1371/journal.pone.0042823}
}
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