The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics
Tang MX, Stern Y, Marder K, Bell K, Gurland B, Lantigua R, Andrews H, Feng L et al.. JAMA, 1998-03-01
Topic: Amyloid, tau and blood-test diagnosis
Context Although the association between Alzheimer disease (AD) and the apolipoprotein E epsilon4 (APOE-epsilon4) allele has been confirmed worldwide, it appears to be inconsistent among African Americans, Hispanics, and Nigerians. Objective To investigate the association between the APOE-epsilon4 allele and AD in elderly African Americans, Hispanics, and whites. Design Prospective, population-based, longitudinal study over a 5-year period (1991-1996). Setting The Washington Heights-Inwood community of New York City. Participants A total of 1079 Medicare recipients without AD or a related disorder at baseline. Main outcome measures Risk of clinically diagnosed AD in the 3 ethnic groups and among individuals with and without an APOE-epsilon4 allele. Results Compared with individuals with the APOE-epsilon3/epsilon3 genotype, the relative risk (RR) of AD associated with 1 or more copies of the APOE-epsilon4 allele was significantly increased among whites (RR, 2.5; 95% confidence interval [CI], 1.1-6.4), but not among African Americans (RR, 1.0; 95% CI, 0.6-1.6) or Hispanics (RR, 1.1; 95% CI, 0.7-1.6). In the absence of the APOE-epsilon4 allele, the cumulative risks of AD to age 90 years, adjusted for education and sex, were 4 times higher for African Americans (RR, 4.4; 95% CI, 2.3-8.6) and 2 times higher for Hispanics (RR, 2.3; 95% CI, 1.2-4.3) than for whites. In the presence of an APOE-epsilon4 allele, the cumulative risk of AD to age 90 years was similar for individuals in all 3 ethnic groups. Conclusion The presence of an APOE-epsilon4 allele is a determinant of AD risk in whites, but African Americans and Hispanics have an increased frequency of AD regardless of their APOE genotype. These results suggest that other genes or risk factors may contribute to the increased risk of AD in African Americans and Hispanics.
Key findings
- Results Compared with individuals with the APOE-epsilon3/epsilon3 genotype, the relative risk (RR) of AD associated with 1 or more copies of the APOE-epsilon4 allele was significantly increased among whites (RR, 2.5; 95% confidence interval [CI], 1.1-6.4), but not among African Americans (RR, 1.0; 95% CI, 0.6-1.6) or Hispanics (RR, 1.1; 95% CI, 0.7-1.6).
- These results suggest that other genes or risk factors may contribute to the increased risk of AD in African Americans and Hispanics.
Why it matters
In 1,079 older Medicare recipients in one New York City community, followed from 1991 to 1996, carrying at least one APOE-ε4 copy (compared with the ε3/ε3 genotype) was linked to a 2.5-fold higher Alzheimer's risk in whites (95% CI 1.1–6.4), but no significant increase was found in African Americans (RR 1.0) or Hispanics (RR 1.1). Among people without ε4, the risk to age 90, adjusted for education and sex, was 4.4 times higher for African Americans and 2.3 times higher for Hispanics than for whites. The authors suggest "other genes or risk factors" may explain this; the study shows associations only, did not identify those factors, and tested no treatment or prevention.
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Study details
- Study designlongitudinal study
- Participants1,079
- Evidence strengthModerate
How this study scored 70/100
Published in a top-tier journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| 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 | 1 / 5 | 1998 — older than 20 years, still counted |
| Sample size | 3 / 4 | 1,079 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 | 6 / 7 | Cited 773 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.8 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 5 / 6 | Cited 24.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 87 other studies in this library |
| Still being cited | 3 / 4 | Cited 82 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ming‐Xin Tang: h-index 49 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Columbia University: institution h-index 1,824 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9508150) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 70 / 100 | — |
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Read the original
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APA 7th
Tang, M. X., Stern, Y., Marder, K., Bell, K., Gurland, B., Lantigua, R., et al. (1998). The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA. https://doi.org/10.1001/jama.279.10.751
Vancouver
Tang MX, Stern Y, Marder K, Bell K, Gurland B, Lantigua R, et al. The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA. 1998. doi:10.1001/jama.279.10.751. PMID: 9508150.
BibTeX
@article{tang1998-9508150,
author = {Tang, M. X. and Stern, Y. and Marder, K. and Bell, K. and Gurland, B. and Lantigua, R. and Andrews, H. and Feng, L. and others},
title = {{The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics}},
journal = {JAMA},
year = {1998},
doi = {10.1001/jama.279.10.751},
pmid = {9508150},
url = {https://doi.org/10.1001/jama.279.10.751}
}
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