Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease
Mandrekar-Colucci S, Karlo JC, Landreth GE.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012-07-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease is associated with a disruption of amyloid β (Aβ) homeostasis, resulting in the accumulation and subsequent deposition of Aβ peptides within the brain. The peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated nuclear receptor that acts in a coupled metabolic cycle with Liver X Receptors (LXRs) to increase brain apolipoprotein E (apoE) levels. apoE functions to promote the proteolytic clearance of soluble forms of Aβ, and we found that the synthetic PPARγ agonist, pioglitazone, stimulated Aβ degradation by both microglia and astrocytes in an LXR and apoE-dependent manner. Remarkably, a brief 9 d oral treatment of APPswe/PS1Δe9 mice with pioglitazone resulted in dramatic reductions in brain levels of soluble and insoluble Aβ levels which correlated with the loss of both diffuse and dense-core plaques within the cortex. The removal of preexisting amyloid deposits was associated with the appearance of abundant Aβ-laden microglia and astrocytes. Pioglitazone treatment resulted in the phenotypic polarization of microglial cells from a proinflammatory M1 state, into an anti-inflammatory M2 state that was associated with enhanced phagocytosis of deposited forms of amyloid. The reduction in amyloid levels was associated with a reversal of contextual memory deficits in the drug-treated mice. These data provide a mechanistic explanation for how PPARγ activation facilitates amyloid clearance and supports the therapeutic utility of PPARγ agonists for the treatment of Alzheimer's disease.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mandrekar-Colucci, S., Karlo, J. C., & Landreth, G. E. (2012). Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.5268-11.2012
Vancouver
Mandrekar-Colucci S, Karlo JC, Landreth GE. Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012. doi:10.1523/jneurosci.5268-11.2012. PMID: 22836247.
BibTeX
@article{mandrekarcolucci2012-22836247,
author = {Mandrekar-Colucci, S. and Karlo, J. C. and Landreth, G. E.},
title = {{Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2012},
doi = {10.1523/jneurosci.5268-11.2012},
pmid = {22836247},
url = {https://doi.org/10.1523/jneurosci.5268-11.2012}
}
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.
Key findings
- Alzheimer's disease is associated with a disruption of amyloid β (Aβ) homeostasis, resulting in the accumulation and subsequent deposition of Aβ peptides within the brain.
- The peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated nuclear receptor that acts in a coupled metabolic cycle with Liver X Receptors (LXRs) to increase brain apolipoprotein E (apoE) levels. apoE functions to promote the proteolytic clearance of soluble forms of Aβ, and we found that the synthetic PPARγ agonist, pioglitazone, stimulated Aβ degradation by both microglia and astrocytes in an LXR and apoE-dependent manner.
- The removal of preexisting amyloid deposits was associated with the appearance of abundant Aβ-laden microglia and astrocytes.
- Pioglitazone treatment resulted in the phenotypic polarization of microglial cells from a proinflammatory M1 state, into an anti-inflammatory M2 state that was associated with enhanced phagocytosis of deposited forms of amyloid.
- The reduction in amyloid levels was associated with a reversal of contextual memory deficits in the drug-treated mice.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 36/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| 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 | 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 “murine”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22836247) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related studies in Genetics
Also tagged “murine”
2 studies in the library carry the topic tag “murine”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 2 tagged studies.