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Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women With Alzheimer's Disease
Paranjpe MD, Belonwu S, Wang JK, Oskotsky T, Gupta A, Taubes A, Zalocusky KA, Paranjpe I et al.. Frontiers in aging neuroscience, 2021-09-30
Topic: Amyloid, tau and blood-test diagnosis
Strikingly gene-expression, network-based analysis and cell type deconvolution approaches revealed a consistent immune signature in the brain and blood of female AD patients that was absent in males. In females, network-based analysis revealed a coordinated program of gene expression involving several zinc finger nuclease genes related to Herpes simplex viral infection whose expression was modulated by the presence of the APOE ε4 allele. Interestingly, this gene expression program was missing in the brains of male AD patients. Cell type deconvolution identified an increase in neutrophils and naïve B cells and a decrease in M2 macrophages, memory B cells, and CD8+ T cells in AD samples compared to controls in females. Interestingly, among males with AD, no significant differences in immune cell proportions compared to controls were observed. Machine learning-based classification of AD using gene expression from whole blood in addition to clinical features produced an improvement in classification accuracy upon stratifying by sex, achieving an AUROC of 0.91 for females and 0.80 for males. These results help identify sex and APOE ε4 genotype-specific transcriptomic signatures of AD and underscore the importance of considering sex in the development of biomarkers and therapeutic strategies for AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Paranjpe, M. D., Belonwu, S., Wang, J. K., Oskotsky, T., Gupta, A., Taubes, A., et al. (2021). Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women With Alzheimer's Disease. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2021.735611
Vancouver
Paranjpe MD, Belonwu S, Wang JK, Oskotsky T, Gupta A, Taubes A, et al. Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women With Alzheimer's Disease. Frontiers in aging neuroscience. 2021. doi:10.3389/fnagi.2021.735611. PMID: 34658838.
BibTeX
@article{paranjpe2021-34658838,
author = {Paranjpe, M. D. and Belonwu, S. and Wang, J. K. and Oskotsky, T. and Gupta, A. and Taubes, A. and Zalocusky, K. A. and Paranjpe, I. and others},
title = {{Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women With Alzheimer's Disease}},
journal = {Frontiers in aging neuroscience},
year = {2021},
doi = {10.3389/fnagi.2021.735611},
pmid = {34658838},
url = {https://doi.org/10.3389/fnagi.2021.735611}
}
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Key findings
- Strikingly gene-expression, network-based analysis and cell type deconvolution approaches revealed a consistent immune signature in the brain and blood of female AD patients that was absent in males.
- In females, network-based analysis revealed a coordinated program of gene expression involving several zinc finger nuclease genes related to Herpes simplex viral infection whose expression was modulated by the presence of the APOE ε4 allele.
- Interestingly, this gene expression program was missing in the brains of male AD patients.
- Cell type deconvolution identified an increase in neutrophils and naïve B cells and a decrease in M2 macrophages, memory B cells, and CD8+ T cells in AD samples compared to controls in females.
- Interestingly, among males with AD, no significant differences in immune cell proportions compared to controls were observed.
Why it matters
This meta-analysis found a consistent immune signature in the brain and blood of female Alzheimer's disease patients that was absent in males, and classification accuracy improved when results were split by sex. These findings are about immune differences and biomarkers and do not test any treatment, cure or prevention.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 63/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 60 of the 96 points we could judge it on, which is 63 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in aging neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Aging Neuroscience: journal h-index 174 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” 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 | A review of other studies — randomisation is not credited here |
| Times cited | 4 / 7 | Cited 50 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 5.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34658838) |
| Free to read | 2 / 2 | Free to read |
| Points | 60 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 60 of the 96 points we could judge it on is 63 out of 100. |
| Total | 63 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fnagi.2021.735611
- PubMed: 34658838
- Original source →
- Free full text: Frontiers in Aging Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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