Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP/PS1 mice
McIntosh A, Mela V, Harty C, Minogue AM, Costello DA, Kerskens C, Lynch MA.. Brain pathology (Zurich, Switzerland), 2019-02-17
Topic: Inflammation, microglia and astrocytes
Plain-language summary
Among the changes that typify Alzheimer's disease (AD) are neuroinflammation and microglial activation, amyloid deposition perhaps resulting from compromised microglial function and iron accumulation. Data from Genome Wide Association Studies (GWAS) identified a number of gene variants that endow a significant risk of developing AD and several of these encode proteins expressed in microglia and proteins that are implicated in the immune response. This suggests that neuroinflammation and the accompanying microglial activation are likely to contribute to the pathogenesis of the disease. The trigger(s) leading to these changes remain to be identified. In this study, we set out to examine the link between the inflammatory, metabolic and iron-retentive signature of microglia in vitro and in transgenic mice that overexpress the amyloid precursor protein (APP) and presenilin 1 (PS1; APP/PS1 mice), a commonly used animal model of AD. Stimulation of cultured microglia with interferon (IFN)γ and amyloid-β (Aβ) induced an inflammatory phenotype and switched the metabolic profile and iron handling of microglia so that the cells became glycolytic and iron retentive, and the phagocytic and chemotactic function of the cells was reduced. Analysis of APP/PS1 mice by magnetic resonance imaging (MRI) revealed genotype-related hypointense areas in the hippocampus consistent with iron deposition, and immunohistochemical analysis indicated that the iron accumulated in microglia, particularly in microglia that decorated Aβ deposits. Isolated microglia prepared from APP/PS1 mice were characterized by a switch to a glycolytic and iron-retentive phenotype and phagocytosis of Aβ was reduced in these cells. This evidence suggests that the switch to glycolysis in microglia may kick-start a cascade of events that ultimately leads to microglial dysfunction and Aβ accumulation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
McIntosh, A., Mela, V., Harty, C., Minogue, A. M., Costello, D. A., Kerskens, C., et al. (2019). Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP/PS1 mice. Brain pathology (Zurich, Switzerland). https://doi.org/10.1111/bpa.12704
Vancouver
McIntosh A, Mela V, Harty C, Minogue AM, Costello DA, Kerskens C, et al. Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP/PS1 mice. Brain pathology (Zurich, Switzerland). 2019. doi:10.1111/bpa.12704. PMID: 30661261.
BibTeX
@article{mcintosh2019-30661261,
author = {McIntosh, A. and Mela, V. and Harty, C. and Minogue, A. M. and Costello, D. A. and Kerskens, C. and Lynch, M. A.},
title = {{Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP/PS1 mice}},
journal = {Brain pathology (Zurich, Switzerland)},
year = {2019},
doi = {10.1111/bpa.12704},
pmid = {30661261},
url = {https://doi.org/10.1111/bpa.12704}
}
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 7 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
- Data from Genome Wide Association Studies (GWAS) identified a number of gene variants that endow a significant risk of developing AD and several of these encode proteins expressed in microglia and proteins that are implicated in the immune response.
- This suggests that neuroinflammation and the accompanying microglial activation are likely to contribute to the pathogenesis of the disease.
- Analysis of APP/PS1 mice by magnetic resonance imaging (MRI) revealed genotype-related hypointense areas in the hippocampus consistent with iron deposition, and immunohistochemical analysis indicated that the iron accumulated in microglia, particularly in microglia that decorated Aβ deposits.
- This evidence suggests that the switch to glycolysis in microglia may kick-start a cascade of events that ultimately leads to microglial dysfunction and Aβ accumulation.
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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 and randomized / 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 multicenter collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain pathology (Zurich, Switzerland)) |
| 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 | 2 / 5 | 2019 — within 10 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 “app/ps1”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30661261) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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