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Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 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, 2021-09-03
Topic: Brain proteins, microglia and lab models
Mechanisms underlying the protective effect of apolipoprotein E (APOE) ε2 against Alzheimer disease (AD) are not well understood. We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ɛ2/ɛ3 carriers. Complement pathway genes C4A and C4B were among the most significantly differentially expressed genes between ɛ2/ɛ3 AD cases and controls.
Key findings
- We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ɛ2/ɛ3 carriers.
- Complement pathway genes C4A and C4B were among the most significantly differentially expressed genes between ɛ2/ɛ3 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 ɛ2 related co-expression network may primarily be involved with tau pathology.
Why it matters
This study analyzed brain tissue from deceased donors and found that complement pathway genes C4A and C4B were among the most differently expressed genes in people with the protective APOE ε2 variant. It is early, laboratory-based work and does not show that targeting these genes would treat or prevent Alzheimer's disease.
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Study details
- Participants982
- Evidence strengthLow
How this study scored 53/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | 3 / 4 | Molecular Psychiatry: journal h-index 318 (OpenAlex, 2026-10-29) |
| 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 | 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 | 4 / 7 | Cited 63 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 37 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Gyungah Jun: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Boston University: institution h-index 1,456 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34480088) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
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Read the original
- DOI: 10.1038/s41380-021-01266-z
- PubMed: 34480088
- Original source →
- Free full text: Molecular Psychiatry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Panitch, R., Hu, J., Chung, J., Zhu, C., Meng, G., Xia, W., et al. (2021). Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease. Molecular psychiatry. https://doi.org/10.1038/s41380-021-01266-z
Vancouver
Panitch R, Hu J, Chung J, Zhu C, Meng G, Xia W, et al. Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease. Molecular psychiatry. 2021. doi:10.1038/s41380-021-01266-z. PMID: 34480088.
BibTeX
@article{panitch2021-34480088,
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 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease}},
journal = {Molecular psychiatry},
year = {2021},
doi = {10.1038/s41380-021-01266-z},
pmid = {34480088},
url = {https://doi.org/10.1038/s41380-021-01266-z}
}
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