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Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer's disease
Serrano-Pozo A, Li Z, Noori A, Nguyen HN, Mezlini A, Li L, Hudry E, Jackson RJ et al.. Nature aging, 2021-10-11
Topic: Amyloid, tau and blood-test diagnosis
The roles of APOE ε4 and APOE ε2-the strongest genetic risk and protective factors for Alzheimer's disease-in glial responses remain elusive. We tested the hypothesis that APOE alleles differentially impact glial responses by investigating their effects on the glial transcriptome from elderly control brains with no neuritic amyloid plaques. We identified a cluster of microglial genes that are upregulated in APOE ε4 and downregulated in APOE ε2 carriers relative to APOE ε3 homozygotes. This microglia- APOE cluster is enriched in phagocytosis-including TREM2 and TYROBP -and proinflammatory genes, and is also detectable in brains with frequent neuritic plaques. Next, we tested these findings in APOE knock-in mice exposed to acute (lipopolysaccharide challenge) and chronic (cerebral β-amyloidosis) insults and found that these mice partially recapitulate human APOE -linked expression patterns. Thus, the APOE ε4 allele might prime microglia towards a phagocytic and proinflammatory state through an APOE-TREM2-TYROBP axis in normal aging as well as in Alzheimer's disease.
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APA 7th
Serrano-Pozo, A., Li, Z., Noori, A., Nguyen, H. N., Mezlini, A., Li, L., et al. (2021). Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer's disease. Nature aging. https://doi.org/10.1038/s43587-021-00123-6
Vancouver
Serrano-Pozo A, Li Z, Noori A, Nguyen HN, Mezlini A, Li L, et al. Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer's disease. Nature aging. 2021. doi:10.1038/s43587-021-00123-6. PMID: 36199750.
BibTeX
@article{serranopozo2021-36199750,
author = {Serrano-Pozo, A. and Li, Z. and Noori, A. and Nguyen, H. N. and Mezlini, A. and Li, L. and Hudry, E. and Jackson, R. J. and others},
title = {{Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer's disease}},
journal = {Nature aging},
year = {2021},
doi = {10.1038/s43587-021-00123-6},
pmid = {36199750},
url = {https://doi.org/10.1038/s43587-021-00123-6}
}
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Key findings
- Next, we tested these findings in APOE knock-in mice exposed to acute (lipopolysaccharide challenge) and chronic (cerebral β-amyloidosis) insults and found that these mice partially recapitulate human APOE -linked expression patterns.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people 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 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| 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 | 2021 — 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 36199750) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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