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A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease
Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S et al.. The Journal of clinical investigation, 2012-03-12
Topic: Brain proteins, microglia and lab models
In Alzheimer disease (AD), amyloid β peptide (Aβ) accumulates in plaques in the brain. Receptor for advanced glycation end products (RAGE) mediates Aβ-induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo.
Key findings
- Receptor for advanced glycation end products (RAGE) mediates Aβ-induced perturbations in cerebral vessels, neurons, and microglia in AD.
- Here, we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo.
- FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB).
- In aged APPsw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibited RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain.
Why it matters
In a mouse model of Alzheimer's disease, a RAGE-specific inhibitor called FPS-ZM1 blocked amyloid-beta binding to RAGE, was nontoxic to mice and crossed the blood-brain barrier, reducing amyloid-beta-mediated brain disorder. This is animal and in-vitro work only and reports no treatment, cure or prevention for people.
Study details
- Evidence strengthLow
How this study scored 54/100
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 Journal of clinical investigation) |
| Journal's citation record | 4 / 4 | Journal of Clinical Investigation: journal h-index 706 (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 620 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 38.8 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 5 / 6 | Cited 23.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 3 / 4 | Cited 109 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Berislav V. Zloković: h-index 118 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Southern California: institution h-index 1,521 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22406537) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Deane, R., Singh, I., Sagare, A. P., Bell, R. D., Ross, N. T., LaRue, B., et al. (2012). A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. The Journal of clinical investigation. https://doi.org/10.1172/jci58642
Vancouver
Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, et al. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. The Journal of clinical investigation. 2012. doi:10.1172/jci58642. PMID: 22406537.
BibTeX
@article{deane2012-22406537,
author = {Deane, R. and Singh, I. and Sagare, A. P. and Bell, R. D. and Ross, N. T. and LaRue, B. and Love, R. and Perry, S. and others},
title = {{A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease}},
journal = {The Journal of clinical investigation},
year = {2012},
doi = {10.1172/jci58642},
pmid = {22406537},
url = {https://doi.org/10.1172/jci58642}
}
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