Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease
Schwab C, Hosokawa M, McGeer PL.. Experimental neurology, 2004-07-01
Topic: Brain proteins, microglia and lab models
We compared lesions in elderly transgenic (tg) mice carrying the Swedish double mutation KM670/671NL with lesions in Alzheimer disease (AD) by histochemical and immunohistochemical techniques. Highly similar staining for beta-amyloid protein (Abeta) was observed in AD and the mouse models. The abundant amyloid deposits in tg mice were in a consolidated state as revealed by strong Congo red birefringence. In both tg mice and AD, amyloid deposits were ApoE-positive and were surrounded by activated astrocytes. However, Bielschowsky silver staining and immunostaining with tau antibodies revealed no neurofibrillary tangles (NFTs) in the mice as opposed to abundant NFTs in AD. The microglial pattern was also distinctly different. Tg mice had only weakly activated microglia, which expressed low levels of the complement receptor CD11b. They were gathered around the periphery of the deposits. In contrast, AD lesions had strongly activated microglia, which expressed high levels of CD11b. They were associated with the plaque core. Immunostaining for complement proteins was weak in tg mice but very strong in AD deposits. We conclude that the weak inflammatory response and absence of NFTs indicate that tg mice are only a limited model of AD. Therapeutic strategies for the treatment of AD based on tg mouse models that overexpress Abeta may be limited in their application.
Key findings
- The abundant amyloid deposits in tg mice were in a consolidated state as revealed by strong Congo red birefringence.
- However, Bielschowsky silver staining and immunostaining with tau antibodies revealed no neurofibrillary tangles (NFTs) in the mice as opposed to abundant NFTs in AD.
- They were associated with the plaque core.
- We conclude that the weak inflammatory response and absence of NFTs indicate that tg mice are only a limited model of AD.
Why it matters
In older mice carrying the Swedish APP mutation, amyloid plaques looked "highly similar" to those in human Alzheimer's, with the same ApoE and astrocyte signs — but the mice had no tau tangles, only weak microglia activation and weak complement staining, where human brains showed strong ones. The authors conclude these mice are "only a limited model of AD," so treatments developed in amyloid-overexpressing mice "may be limited in their application" to people. No treatment was tested in this study.
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Study details
- Evidence strengthLow
How this study scored 42/100
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 (Experimental neurology) |
| Journal's citation record | 3 / 4 | Experimental Neurology: journal h-index 271 (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 | 2004 — older than 20 years, still counted |
| 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 “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 125 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.2 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 3 / 6 | Cited 7.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Patrick L. McGeer: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of British Columbia: institution h-index 1,424 (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 15191802) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
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May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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. Check the citation against the original before you use it.
APA 7th
Schwab, C., Hosokawa, M., & McGeer, P. L. (2004). Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Experimental neurology. https://doi.org/10.1016/j.expneurol.2004.03.016
Vancouver
Schwab C, Hosokawa M, McGeer PL. Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Experimental neurology. 2004. doi:10.1016/j.expneurol.2004.03.016. PMID: 15191802.
BibTeX
@article{schwab2004-15191802,
author = {Schwab, C. and Hosokawa, M. and McGeer, P. L.},
title = {{Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease}},
journal = {Experimental neurology},
year = {2004},
doi = {10.1016/j.expneurol.2004.03.016},
pmid = {15191802},
url = {https://doi.org/10.1016/j.expneurol.2004.03.016}
}
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