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Metallothionein-I and -III expression in animal models of Alzheimer disease
Carrasco J, Adlard P, Cotman C, Quintana A, Penkowa M, Xu F, Van Nostrand WE, Hidalgo J.. Neuroscience, 2006-10-04
Topic: Amyloid, tau and blood-test diagnosis
Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta) deposition within the brain. We have evaluated the expression of MT-I and MT-III mRNA by in situ hybridization in three different transgenic mice models of AD: Tg2576 (carrying AbetaPP harboring the Swedish K670N/M671L mutations), TgCRND8 (Swedish and the Indiana V717F mutations), and Tg-SwDI (Swedish and Dutch/Iowa E693Q/D694N mutations). MT-I mRNA levels were induced in all transgenic lines studied, although the pattern of induction differed between the models. In the Tg2576 mice MT-I was weakly upregulated in cells surrounding Congo Red-positive plaques in the cortex and hippocampus. A more potent induction of MT-I was observed in the cortex and hippocampus of the TgCRND8 mice, likely reflecting their higher amyloid plaques content. MT-I upregulation was also more significant in Tg-SwDI mice, especially in the subiculum and hippocampus CA1 area. Immunofluorescence stainings demonstrate that astrocytes and microglia/macrophages surrounding the plaques express MT-I&II. In general, MT-I regulation follows a similar but less potent response than glial fibrillary acidic protein (GFAP) expression. In contrast to MT-I, MT-III mRNA expression was not significantly altered in any of the models examined suggesting that the various MT isoforms may have different roles in these experimental systems, and perhaps also in human AD.
Key findings
- These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta) deposition within the brain.
- MT-I upregulation was also more significant in Tg-SwDI mice, especially in the subiculum and hippocampus CA1 area.
- In contrast to MT-I, MT-III mRNA expression was not significantly altered in any of the models examined suggesting that the various MT isoforms may have different roles in these experimental systems, and perhaps also in human AD.
Why it matters
In three transgenic mouse models of Alzheimer disease amyloid deposits, MT-I mRNA was induced in all lines though the pattern differed, while MT-III mRNA expression was not significantly altered in any model. These animal findings suggest different metallothionein isoforms may have different roles in these models, but they do not establish any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuroscience) |
| Journal's citation record | 3 / 4 | Neuroscience: journal h-index 370 (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 | 2006 — 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 60 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 2 / 6 | Cited 2.4× 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 | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Juan Hidalgo: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Copenhagen: institution h-index 1,378 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17027170) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 38 / 100 | — |
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Read the original
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. The record names 8 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.
APA 7th
Carrasco, J., Adlard, P., Cotman, C., Quintana, A., Penkowa, M., Xu, F., et al. (2006). Metallothionein-I and -III expression in animal models of Alzheimer disease. Neuroscience. https://doi.org/10.1016/j.neuroscience.2006.08.054
Vancouver
Carrasco J, Adlard P, Cotman C, Quintana A, Penkowa M, Xu F, et al. Metallothionein-I and -III expression in animal models of Alzheimer disease. Neuroscience. 2006. doi:10.1016/j.neuroscience.2006.08.054. PMID: 17027170.
BibTeX
@article{carrasco2006-17027170,
author = {Carrasco, J. and Adlard, P. and Cotman, C. and Quintana, A. and Penkowa, M. and Xu, F. and Van Nostrand, W. E. and Hidalgo, J.},
title = {{Metallothionein-I and -III expression in animal models of Alzheimer disease}},
journal = {Neuroscience},
year = {2006},
doi = {10.1016/j.neuroscience.2006.08.054},
pmid = {17027170},
url = {https://doi.org/10.1016/j.neuroscience.2006.08.054}
}
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