A common 19 bp APOE enhancer deletion is protective against Alzheimer's disease in African Americans
Brutman JN, Busald T, Nizamis E, Kaufman EJ, Lin E, Hendricks NE, Chintamen S, Sulovari A, Smukowski SN, Ye Y, Peikon I, Jayadev S, et al.. Nature Communications, 2026-02-02
Topic: Amyloid, tau and blood-test diagnosis
The APOE-ε4/ε4 genotype is the strongest genetic risk factor for sporadic Alzheimer's disease, though the relative risk is diminished in individuals with African ancestry. Through analysis of phased APOE alleles, we identify a 19 bp deletion approximately 1.1 kb distal to the APOE 3'UTR in a SPI1 microglial transcription factor binding site. The deletion is present in 60% of African American APOE-ε4 homozygotes and reduces Alzheimer's disease odds ratio relative to individuals without the deletion. The deletion also delays Alzheimer's disease onset in APOE-ε4/ε4 cases with local African ancestry at APOE. The All of Us dataset confirms reduced Alzheimer´s disease risk associated with the deletion and identifies additional variants between APOE and APOC1 that disentangle APOE-ε4 neurological and lipid-related phenotypes. Functional assays reveal that the 19 bp deletion abolishes SPI1 repression at this region. Collectively, these findings describe a protective allele at APOE in African Americans that mediates APOC1 expression, reducing relative Alzheimer´s disease risk.
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APA 7th
Brutman, J. N., Busald, T., Nizamis, E., Kaufman, E. J., Lin, E., Hendricks, N. E., et al. (2026). A common 19 bp APOE enhancer deletion is protective against Alzheimer's disease in African Americans. Nature Communications. https://doi.org/10.1038/s41467-026-68808-3
Vancouver
Brutman JN, Busald T, Nizamis E, Kaufman EJ, Lin E, Hendricks NE, et al. A common 19 bp APOE enhancer deletion is protective against Alzheimer's disease in African Americans. Nature Communications. 2026. doi:10.1038/s41467-026-68808-3. PMID: 41629326.
BibTeX
@article{brutman2026-41629326,
author = {Brutman, J. N. and Busald, T. and Nizamis, E. and Kaufman, E. J. and Lin, E. and Hendricks, N. E. and Chintamen, S. and Sulovari, A. and Smukowski, S. N. and Ye, Y. and Peikon, I. and Jayadev, S. and others},
title = {{A common 19 bp APOE enhancer deletion is protective against Alzheimer's disease in African Americans}},
journal = {Nature Communications},
year = {2026},
doi = {10.1038/s41467-026-68808-3},
pmid = {41629326},
url = {https://doi.org/10.1038/s41467-026-68808-3}
}
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Key findings
- The All of Us dataset confirms reduced Alzheimer´s disease risk associated with the deletion and identifies additional variants between APOE and APOC1 that disentangle APOE-ε4 neurological and lipid-related phenotypes.
- Collectively, these findings describe a protective allele at APOE in African Americans that mediates APOC1 expression, reducing relative Alzheimer´s disease risk.
Why it matters
A 19 base pair deletion near APOE was linked to lower Alzheimer's risk and later onset in African American APOE-ε4 carriers. This is a genetic finding about risk, not a treatment or prevention method.
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Study details
- Study designcase-control
- Evidence strengthModerate
Limitations
The authors note that the GTEx expression-quantitative-trait finding for this variant rests on only four heterozygous samples, and that whether single-cell datasets showing ancestry-specific APOE expression differences included the deletion allele is unknown.
How this study scored 57/100
Published in a leading specialty journal, and it is a case-control study. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 56 of the 98 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29) |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 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 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 29.0× 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 | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Paul N. Valdmanis: h-index 32 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41629326) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 56 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 56 of the 98 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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