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Ancestry-specific effects of APOE on Alzheimer Disease Endophenotypes
Boeriu, A. I.; Gu, T.; Fulton-Howard, B.; Lucero, E. M.; Garg, P.; Sharp, A.; Shortt, J. A.; Gignoux et al.. medRxiv (preprint), 2026-09-05
Topic: Amyloid, tau and blood-test diagnosis
INTRODUCTIONAPOE*{varepsilon}4 is the strongest genetic risk factor for Alzheimers disease (AD), yet its effect varies across ancestral populations. As plasma biomarkers increasingly inform AD diagnosis, failure to account for both APOE genotype and genetic ancestry could lead to diagnostic misclassification. METHODSIn 2,733 participants from the Health and Aging Brain Study-Health Disparities (HABS-HD), we evaluated whether genetically-inferred ancestry modifies APOE associations with AD endophenotypes. Regression models were applied across three frameworks: ancestry-stratified analyses, compositional modeling of global ancestry, and local ancestry analyses at the APOE locus. RESULTSAPOE {varepsilon}4+ was associated with higher pTau217 and pTau181, lower A{beta}42/A{beta}40, and worse global cognition (CDR-SB), significant within ancestry groups after FDR correction. The {varepsilon}4+ effect on pTau217 was [~]2.5-fold larger in EUR-like than AFR-like participants. DISCUSSIONAfrican ancestry attenuates APOE*{varepsilon}4+ associations with pTau217, highlighting the need to consider both APOE genotype and ancestry in biomarker-based AD evaluations.
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APA 7th
Boeriu, A. I., Gu, T., Fulton-Howard, B., Lucero, E. M., Garg, P., Sharp, A., et al. (2026). Ancestry-specific effects of APOE on Alzheimer Disease Endophenotypes. medRxiv (preprint). https://doi.org/10.64898/2026.03.23.26349095
Vancouver
Boeriu AI, Gu T, Fulton-Howard B, Lucero EM, Garg P, Sharp A, et al. Ancestry-specific effects of APOE on Alzheimer Disease Endophenotypes. medRxiv (preprint). 2026. doi:10.64898/2026.03.23.26349095.
BibTeX
@article{boeriu2026-52d13682,
author = {Boeriu, A. I. and Gu, T. and Fulton-Howard, B. and Lucero, E. M. and Garg, P. and Sharp, A. and Shortt, J. A. and Gignoux and others},
title = {{Ancestry-specific effects of APOE on Alzheimer Disease Endophenotypes}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.03.23.26349095},
url = {https://doi.org/10.64898/2026.03.23.26349095}
}
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Key findings
- RESULTSAPOE {varepsilon}4+ was associated with higher pTau217 and pTau181, lower A{beta}42/A{beta}40, and worse global cognition (CDR-SB), significant within ancestry groups after FDR correction.
Why it matters
This study found that the APOE e4 effect on pTau217 was about 2.5-fold larger in participants of European-like ancestry than African-like ancestry, and that African ancestry weakened these associations. It concerns how genetic ancestry affects biomarker interpretation and does not test any treatment, cure or prevention.
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Study details
- Participants2,733
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 31 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 29 of the 94 points we could judge it on, which is 31 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,733 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 | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 2 year(s) since 2026 |
| 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Shea J. Andrews: h-index 34 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 29 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 29 of the 94 points we could judge it on is 31 out of 100. |
| Total | 31 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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