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Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries
Xu X, Kwon J, Yan R, Apio C, Song S, Heo G, Yang Q, Timsina J et al.. JAMA network open, 2025-03-03
Topic: Amyloid, tau and blood-test diagnosis
Importance Age, sex, and apolipoprotein E (APOE) are the strongest risk factors for late-onset Alzheimer disease (AD). The role of APOE in AD varies with sex and ancestry. While the association of APOE with AD biomarkers also varies across sex and ancestry, no study has systematically investigated both sex-specific and ancestry differences of APOE on cerebrospinal fluid (CSF) biomarkers together, resulting in limited insights and generalizability.
Key findings
- The role of APOE in AD varies with sex and ancestry.
- While the association of APOE with AD biomarkers also varies across sex and ancestry, no study has systematically investigated both sex-specific and ancestry differences of APOE on cerebrospinal fluid (CSF) biomarkers together, resulting in limited insights and generalizability.
- Objective To systematically investigate the association of sex and APOE-ε4 with 3 core CSF biomarkers across ancestries.
- Design, setting, and participants This cohort study examined 3 CSF biomarkers (amyloid β1-42 [Aβ42], phosphorylated tau 181 [p-tau], and total tau, in participants from 20 cohorts from July 1, 1985, to March 31, 2020.
Why it matters
This meta-analysis examined how the APOE gene, sex and ancestry relate to three core CSF Alzheimer's biomarkers. It is about understanding risk and biomarker patterns across groups, not about treating or preventing Alzheimer's.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designmeta-analysis
- Participants4,592
- Effect size52.8%; 2.6%; 1.1%
- Evidence strengthHigh
How this study scored 76/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. We have no data on senior author's track record, so that was left out: it earned 73 of the 96 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA network open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 4,592 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 3 / 7 | Cited 24 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 13.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 24 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 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 19 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40067298) |
| Free to read | 2 / 2 | Free to read |
| Points | 73 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 73 of the 96 points we could judge it on is 76 out of 100. |
| Total | 76 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamanetworkopen.2025.0562
- PubMed: 40067298
- Original source →
- Free full text: JAMA Network Open →
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
Xu, X., Kwon, J., Yan, R., Apio, C., Song, S., Heo, G., et al. (2025). Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries. JAMA network open. https://doi.org/10.1001/jamanetworkopen.2025.0562
Vancouver
Xu X, Kwon J, Yan R, Apio C, Song S, Heo G, et al. Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries. JAMA network open. 2025. doi:10.1001/jamanetworkopen.2025.0562. PMID: 40067298.
BibTeX
@article{xu2025-40067298,
author = {Xu, X. and Kwon, J. and Yan, R. and Apio, C. and Song, S. and Heo, G. and Yang, Q. and Timsina, J. and others},
title = {{Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries}},
journal = {JAMA network open},
year = {2025},
doi = {10.1001/jamanetworkopen.2025.0562},
pmid = {40067298},
url = {https://doi.org/10.1001/jamanetworkopen.2025.0562}
}
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