Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds
Griswold AJ, Celis K, Bussies PL, Rajabli F, Whitehead PL, Hamilton-Nelson KL, Beecham GW, Dykxhoorn DM et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2021-02-01
Topic: Amyloid, tau and blood-test diagnosis
Introduction Apolipoprotein E (APOE) ε4 confers less risk for Alzheimer's disease (AD) in carriers with African local genomic ancestry (ALA) than APOE ε4 carriers with European local ancestry (ELA). Cell type specific transcriptional variation between the two local ancestries (LAs) could contribute to this disease risk differences. Methods Single-nucleus RNA sequencing was performed on frozen frontal cortex of homozygous APOE ε4/ε4 AD patients: seven with ELA, four with ALA. Results A total of 60,908 nuclei were sequenced. Within the LA region (chr19:44-46Mb), APOE was the gene most differentially expressed, with ELA carriers having significantly more expression (overall P -317 ) in 24 of 32 cell clusters. The transcriptome of one astrocyte cluster, with high APOE ε4 expression and specific to ELA, is suggestive of A1 reactive astrocytes. Discussion AD patients with ELA expressed significantly greater levels of APOE than ALA APOE ε4 carriers. These differences in APOE expression could contribute to the reduced risk for AD seen in African APOE ε4 carriers.
Key findings
- Results A total of 60,908 nuclei were sequenced.
- Within the LA region (chr19:44-46Mb), APOE was the gene most differentially expressed, with ELA carriers having significantly more expression (overall P -317 ) in 24 of 32 cell clusters.
- Discussion AD patients with ELA expressed significantly greater levels of APOE than ALA APOE ε4 carriers.
Why it matters
This single-nucleus RNA sequencing study found that Alzheimer disease patients with European local ancestry expressed more APOE than those with African local ancestry. The authors suggest these expression differences could contribute to the reduced risk seen in African APOE ε4 carriers, but this is a preliminary finding needing further study.
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Study details
- Participants60,908
- Evidence strengthLow
How this study scored 57/100
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 (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 4 / 4 | 60,908 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 89 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.7 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 6.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 57 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jeffery M. Vance: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Northwestern University: institution h-index 1,592 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33522086) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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Read the original
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APA 7th
Griswold, A. J., Celis, K., Bussies, P. L., Rajabli, F., Whitehead, P. L., Hamilton-Nelson, K. L., et al. (2021). Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.12287
Vancouver
Griswold AJ, Celis K, Bussies PL, Rajabli F, Whitehead PL, Hamilton-Nelson KL, et al. Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021. doi:10.1002/alz.12287. PMID: 33522086.
BibTeX
@article{griswold2021-33522086,
author = {Griswold, A. J. and Celis, K. and Bussies, P. L. and Rajabli, F. and Whitehead, P. L. and Hamilton-Nelson, K. L. and Beecham, G. W. and Dykxhoorn, D. M. and others},
title = {{Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2021},
doi = {10.1002/alz.12287},
pmid = {33522086},
url = {https://doi.org/10.1002/alz.12287}
}
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