Home › Research › Biomarkers
Dimebon alters hippocampal amyloid pathology in 3xTg-AD mice
Perez SE, Nadeem M, Sadleir KR, Matras J, Kelley CM, Counts SE, Vassar R, Mufson EJ.. International journal of physiology, pathophysiology and pharmacology, 2012-09-20
Topic: Brain proteins, microglia and lab models
A double blind, placebo-controlled phase II study revealed that the antihistamine, Dimebon® (dimebolin, latrepirdine) improved cognition in Alzheimer disease (AD) patients compared to placebo controls. However, the Phase III CONNECTION trial failed to demonstrate significant differences between dimebon and placebo treatments. Despite the controversial therapeutic outcomes in the treatment of AD, dimebon's mechanism(s) of action within the brain remain unclear. In the present study, we evaluated the effects of dimebon upon β-amyloid (Aβ), tau and astrocytes in the hippocampus of triple transgenic (3xTg-AD) mice, which develop AD-like pathology in an age-dependent manner. At age 6.5 months, prior to the development of Aβ plaques in the hippocampus, male and female 3xTg-AD mice, received a daily intraperitoneal injection of 0.1 % dimebon or saline for 1.5 months. At 8 months, quantitative immunohistochemistry revealed a significant reduction in hippocampal/subicular APP/Aβ in dimebon-treated mice, whereas protein bioassay found no change in full length APP, soluble Aβ(1-40) and Aβ(1-42), Aβ oligomers, BACE1 and GFAP levels between groups. Interestingly, the number of the hippocampal APP/Aβ plaques in female and male dimebon-treated mice was higher compared to gender-matched control mice. Dimebon did not alter hippocampal tau levels. Furthermore, dimebon protects SH-SY5Y neurons against Aβ toxicity and promotes GFAP expression in primary mouse astrocyte cultures. Our findings demonstrate that dimebon in vivo modifies hippocampal APP/Aβ pathology and in vitro protects against Aβ toxicity promoting cell survival and activates astrocytes.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Perez, S. E., Nadeem, M., Sadleir, K. R., Matras, J., Kelley, C. M., Counts, S. E., et al. (2012). Dimebon alters hippocampal amyloid pathology in 3xTg-AD mice. International journal of physiology, pathophysiology and pharmacology.
Vancouver
Perez SE, Nadeem M, Sadleir KR, Matras J, Kelley CM, Counts SE, et al. Dimebon alters hippocampal amyloid pathology in 3xTg-AD mice. International journal of physiology, pathophysiology and pharmacology. 2012. PMID: 23071869.
BibTeX
@article{perez2012-23071869,
author = {Perez, S. E. and Nadeem, M. and Sadleir, K. R. and Matras, J. and Kelley, C. M. and Counts, S. E. and Vassar, R. and Mufson, E. J.},
title = {{Dimebon alters hippocampal amyloid pathology in 3xTg-AD mice}},
journal = {International journal of physiology, pathophysiology and pharmacology},
year = {2012},
pmid = {23071869}
}
Built from the record alzhub holds for this paper, not looked up. This record has no DOI, so the citation leaves it out. 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.
Key findings
- A double blind, placebo-controlled phase II study revealed that the antihistamine, Dimebon® (dimebolin, latrepirdine) improved cognition in Alzheimer disease (AD) patients compared to placebo controls.
- However, the Phase III CONNECTION trial failed to demonstrate significant differences between dimebon and placebo treatments.
- At 8 months, quantitative immunohistochemistry revealed a significant reduction in hippocampal/subicular APP/Aβ in dimebon-treated mice, whereas protein bioassay found no change in full length APP, soluble Aβ(1-40) and Aβ(1-42), Aβ oligomers, BACE1 and GFAP levels between groups.
- Interestingly, the number of the hippocampal APP/Aβ plaques in female and male dimebon-treated mice was higher compared to gender-matched control mice.
- Our findings demonstrate that dimebon in vivo modifies hippocampal APP/Aβ pathology and in vitro protects against Aβ toxicity promoting cell survival and activates astrocytes.
Why it matters
In 3xTg-AD mice, dimebon reduced hippocampal APP/Aβ by immunohistochemistry but did not change full-length APP, soluble Aβ, oligomers, BACE1 or GFAP, and actually increased the number of APP/Aβ plaques; it also did not alter tau. A phase III trial of dimebon had already failed to show significant differences from placebo, so this does not support dimebon as an effective treatment.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Effect sizeor 1.5
- Evidence strengthLow
How this study scored 34/100
Published in a peer-reviewed journal. Scored zero for study design, sample size and randomized / blinded because the record does not state it. We have no data on journal's citation record, so that was left out: it earned 33 of the 96 points we could judge it on, which is 34 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International journal of physiology, pathophysiology and pharmacology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “3xtg”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 26 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.6 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 2 / 6 | Cited 2.8× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Elliott Jay Mufson: h-index 103 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Rush University Medical Center: institution h-index 670 (OpenAlex) |
| Multicenter 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 23071869) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 33 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 33 of the 96 points we could judge it on is 34 out of 100. |
| Total | 34 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Biomarkers
Also tagged “tdp-43”
1,150 studies in the library carry the topic tag “tdp-43”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.