Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice
Andreas Giannisis, Kalicharan Patra, Anna K Edlund, Lur Agirrezabala Nieto, Joan Benedicto-Gras, Simon Moussaud, Andrés de la Rosa, Daniel Twohig et al.. Molecular psychiatry, 2022-04-13
Topic: Genetics and APOE
Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer's disease (AD) risk and AD biomarker levels. Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 liver phenotype promotes neurodegeneration is unknown. Here we investigated the brains of Fah-/-, Rag2-/-, Il2rg-/- mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEε4-associated risk of neurodegenerative disease.
Key findings
- Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers.
- Here we investigated the brains of Fah-/-, Rag2-/-, Il2rg-/- mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype.
- Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers.
- These results propose a previously unexplored role of the liver in the APOEε4-associated risk of neurodegenerative disease.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a leading specialty 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 25 of the 56 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| 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 | 3 / 5 | 2022 — within 6 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 “mice”) — 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 35418601) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 25 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 25 of the 56 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Giannisis, A., Patra, K., Edlund, A. K., Nieto, L. A., Benedicto-Gras, J., Moussaud, S., et al. (2022). Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice. Molecular psychiatry. https://doi.org/10.1038/s41380-022-01548-0
Vancouver
Giannisis A, Patra K, Edlund AK, Nieto LA, Benedicto-Gras J, Moussaud S, et al. Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice. Molecular psychiatry. 2022. doi:10.1038/s41380-022-01548-0. PMID: 35418601.
BibTeX
@article{giannisis2022-35418601,
author = {Giannisis, Andreas and Patra, Kalicharan and Edlund, Anna K and Nieto, Lur Agirrezabala and Benedicto-Gras, Joan and Moussaud, Simon and de la Rosa, Andrés and Twohig, Daniel and others},
title = {{Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice}},
journal = {Molecular psychiatry},
year = {2022},
doi = {10.1038/s41380-022-01548-0},
pmid = {35418601},
url = {https://doi.org/10.1038/s41380-022-01548-0}
}
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