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Integrative Brain Transcriptome Analysis Links Complement Component 4 andHSPA2to theAPOEε2 Protective Effect in Alzheimer Disease
Panitch R, Hu J, Chung J, Zhu C, Meng G, Xia W, Bennett DA, Lunetta KL et al.. Molecular psychiatry, 2020-11-24
Topic: Brain proteins, microglia and lab models
Mechanisms underlying the protective effect of apolipoprotein E ( APOE ) ε2 against Alzheimer’s disease (AD) are not well understood. We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ε 2/ε 3 carriers. Complement pathway genes C4A and C4B were among the most significantly differentially expressed genes between ε 2/ε 3 AD cases and controls.
Key findings
- We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ε 2/ε 3 carriers.
- Complement pathway genes C4A and C4B were among the most significantly differentially expressed genes between ε 2/ε 3 AD cases and controls.
- We also identified an APOE ε2/ε3 AD-specific co-expression network enriched for astrocytes, oligodendrocytes and oligodendrocyte progenitor cells containing the genes C4A, C4B , and HSPA2 .
- These genes were significantly associated with the ratio of phosphorylated tau at position 231 to total Tau but not with amyloid-β 42 level, suggesting this APOE ε 2 related co-expression network may primarily be involved with tau pathology.
Why it matters
By analyzing brain gene expression from 982 autopsied donors, including 135 APOE ε2/ε3 carriers, this study linked complement pathway genes C4A and C4B and the gene HSPA2 to the protective effect of APOE ε2 against Alzheimer's disease. These findings point to possible biological pathways behind protection, but they come from donated brain tissue and do not establish a treatment or prevention.
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Study details
- Participants982
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, 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, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 30 of the 64 points we could judge it on, which is 47 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 | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 982 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 | 1 / 6 | Cited by 1 other studies in this library |
| 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 34480088) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 30 / 64 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 30 of the 64 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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APA 7th
Panitch, R., Hu, J., Chung, J., Zhu, C., Meng, G., Xia, W., et al. (2020). Integrative Brain Transcriptome Analysis Links Complement Component 4 andHSPA2to theAPOEε2 Protective Effect in Alzheimer Disease. Molecular psychiatry. https://doi.org/10.1101/2020.11.23.20235762
Vancouver
Panitch R, Hu J, Chung J, Zhu C, Meng G, Xia W, et al. Integrative Brain Transcriptome Analysis Links Complement Component 4 andHSPA2to theAPOEε2 Protective Effect in Alzheimer Disease. Molecular psychiatry. 2020. doi:10.1101/2020.11.23.20235762.
BibTeX
@article{panitch2020-51e773db,
author = {Panitch, R. and Hu, J. and Chung, J. and Zhu, C. and Meng, G. and Xia, W. and Bennett, D. A. and Lunetta, K. L. and others},
title = {{Integrative Brain Transcriptome Analysis Links Complement Component 4 andHSPA2to theAPOEε2 Protective Effect in Alzheimer Disease}},
journal = {Molecular psychiatry},
year = {2020},
doi = {10.1101/2020.11.23.20235762},
url = {https://doi.org/10.1101/2020.11.23.20235762}
}
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