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Pyroglutamate-3 amyloid-β deposition in the brains of humans, non-human primates, canines, and Alzheimer disease-like transgenic mouse models
Frost JL, Le KX, Cynis H, Ekpo E, Kleinschmidt M, Palmour RM, Ervin FR, Snigdha S et al.. The American journal of pathology, 2013-06-07
Topic: Brain proteins, microglia and lab models
Amyloid-β (Aβ) peptides, starting with pyroglutamate at the third residue (pyroGlu-3 Aβ), are a major species deposited in the brain of Alzheimer disease (AD) patients. Recent studies suggest that this isoform shows higher toxicity and amyloidogenecity when compared to full-length Aβ peptides. Here, we report the first comprehensive and comparative IHC evaluation of pyroGlu-3 Aβ deposition in humans and animal models. PyroGlu-3 Aβ immunoreactivity (IR) is abundant in plaques and cerebral amyloid angiopathy of AD and Down syndrome patients, colocalizing with general Aβ IR. PyroGlu-3 Aβ is further present in two nontransgenic mammalian models of cerebral amyloidosis, Caribbean vervets, and beagle canines. In addition, pyroGlu-3 Aβ deposition was analyzed in 12 different AD-like transgenic mouse models. In contrast to humans, all transgenic models showed general Aβ deposition preceding pyroGlu-3 Aβ deposition. The findings varied greatly among the mouse models concerning age of onset and cortical brain region. In summary, pyroGlu-3 Aβ is a major species of β-amyloid deposited early in diffuse and focal plaques and cerebral amyloid angiopathy in humans and nonhuman primates, whereas it is deposited later in a subset of focal and vascular amyloid in AD-like transgenic mouse models. Given the proposed decisive role of pyroGlu-3 Aβ peptides for the development of human AD pathology, this study provides insights into the usage of animal models in AD studies.
Key findings
- Recent studies suggest that this isoform shows higher toxicity and amyloidogenecity when compared to full-length Aβ peptides.
Why it matters
This comparative tissue study found that pyroGlu-3 amyloid-beta is deposited early in plaques and cerebral amyloid angiopathy in humans and non-human primates, but later in a subset of amyloid in Alzheimer-like transgenic mouse models. It describes a form of amyloid that may be more toxic and amyloidogenic, but reports no treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 47/100
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 (The American journal of pathology) |
| Journal's citation record | 3 / 4 | American Journal Of Pathology: journal h-index 328 (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 | 2013 — 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 “non-human primates”) — 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 133 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.9 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 3 / 6 | Cited 7.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 20 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Cynthia Ann Lemere: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23747948) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.ajpath.2013.05.005
- PubMed: 23747948
- Original source →
- Free full text: American Journal Of Pathology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Frost, J. L., Le, K. X., Cynis, H., Ekpo, E., Kleinschmidt, M., Palmour, R. M., et al. (2013). Pyroglutamate-3 amyloid-β deposition in the brains of humans, non-human primates, canines, and Alzheimer disease-like transgenic mouse models. The American journal of pathology. https://doi.org/10.1016/j.ajpath.2013.05.005
Vancouver
Frost JL, Le KX, Cynis H, Ekpo E, Kleinschmidt M, Palmour RM, et al. Pyroglutamate-3 amyloid-β deposition in the brains of humans, non-human primates, canines, and Alzheimer disease-like transgenic mouse models. The American journal of pathology. 2013. doi:10.1016/j.ajpath.2013.05.005. PMID: 23747948.
BibTeX
@article{frost2013-23747948,
author = {Frost, J. L. and Le, K. X. and Cynis, H. and Ekpo, E. and Kleinschmidt, M. and Palmour, R. M. and Ervin, F. R. and Snigdha, S. and others},
title = {{Pyroglutamate-3 amyloid-β deposition in the brains of humans, non-human primates, canines, and Alzheimer disease-like transgenic mouse models}},
journal = {The American journal of pathology},
year = {2013},
doi = {10.1016/j.ajpath.2013.05.005},
pmid = {23747948},
url = {https://doi.org/10.1016/j.ajpath.2013.05.005}
}
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