Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain
Nathan R Zuniga, Noah E Earls, Ariel E A Denos, Jared M Elison, Benjamin S Jones, Ethan G Smith, Noah G Moran, Katie L Broce et al.. PLoS computational biology, 2024-12-12
Topic: Genetics and APOE
Apolipoprotein E (ApoE) polymorphisms modify the risk of Alzheimer's disease with ApoE4 strongly increasing and ApoE2 modestly decreasing risk relative to the control ApoE3. To investigate how ApoE isoforms alter risk, we measured changes in proteome homeostasis in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). The regulation of each protein's homeostasis is observed by measuring turnover rate and abundance for that protein. We identified 4849 proteins and tested for ApoE isoform-dependent changes in the homeostatic regulation of ~2700 ontologies. In the brain, we found that ApoE4 and ApoE2 both lead to modified regulation of mitochondrial membrane proteins relative to the wild-type control ApoE3. In ApoE4 mice, lack of cohesion between mitochondrial membrane and matrix proteins suggests that dysregulation of proteasome and autophagy is reducing protein quality. In ApoE2, proteins of the mitochondrial matrix and the membrane, including oxidative phosphorylation complexes, had a similar increase in degradation which suggests coordinated replacement of the entire organelle. In the liver we did not observe these changes suggesting that the ApoE-effect on proteostasis is amplified in the brain relative to other tissues. Our findings underscore the utility of combining protein abundance and turnover rates to decipher proteome regulatory mechanisms and their potential role in biology.
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APA 7th
Zuniga, N. R., Earls, N. E., Denos, A. E. A., Elison, J. M., Jones, B. S., Smith, E. G., et al. (2024). Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain. PLoS computational biology. https://doi.org/10.1371/journal.pcbi.1012407
Vancouver
Zuniga NR, Earls NE, Denos AEA, Elison JM, Jones BS, Smith EG, et al. Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain. PLoS computational biology. 2024. doi:10.1371/journal.pcbi.1012407. PMID: 39666759.
BibTeX
@article{zuniga2024-39666759,
author = {Zuniga, Nathan R and Earls, Noah E and Denos, Ariel E A and Elison, Jared M and Jones, Benjamin S and Smith, Ethan G and Moran, Noah G and Broce, Katie L and others},
title = {{Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain}},
journal = {PLoS computational biology},
year = {2024},
doi = {10.1371/journal.pcbi.1012407},
pmid = {39666759},
url = {https://doi.org/10.1371/journal.pcbi.1012407}
}
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Key findings
- In the brain, we found that ApoE4 and ApoE2 both lead to modified regulation of mitochondrial membrane proteins relative to the wild-type control ApoE3.
- In ApoE4 mice, lack of cohesion between mitochondrial membrane and matrix proteins suggests that dysregulation of proteasome and autophagy is reducing protein quality.
- In the liver we did not observe these changes suggesting that the ApoE-effect on proteostasis is amplified in the brain relative to other tissues.
- Our findings underscore the utility of combining protein abundance and turnover rates to decipher proteome regulatory mechanisms and their potential role in biology.
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Study details
- Evidence strengthLow
How this study scored 43/100
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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PLoS computational biology) |
| 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 | 4 / 5 | 2024 — within 3 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 | — / 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 39666759) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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