Topic: Amyloid, tau and blood-test diagnosis
Carriers of the apolipoprotein E (APOE) epsilon4 allele show significantly higher risk of Alzheimer disease (AD). The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD. Interactions of epsilon4 by gender, although indicated in the literature, require further verification. A total of 195 past or current control or AD participants in an ongoing longitudinal study of aging and dementia were genotyped. All subjects were at least 60 years old; demented subjects met clinical or pathologic criteria for late-onset AD. Logistic regression analysis and proportional hazard models were used to evaluate joint effects of APOE and gender. A significant statistical interaction between APOE and gender was shown (p = 0.04) in logistic regression analysis. Women carrying one or more APOE-epsilon4 allele were more likely to develop AD [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 3.2-19. 1]. For men, the presence of the APOE-epsilon4 allele was not associated with a statistically significant increased risk (OR = 1.6, 95% CI = 0.5-5.3). The interaction term in the proportional hazards model neared (p = 0.07) statistical significance, and a similar but reduced gender effect was shown. The analysis suggests that the presence of one or more APOE-epsilon4 allele confers a substantially greater risk of AD to women than to men. These findings in part may account for reports of increased risk of AD faced by women.
Key findings
- Carriers of the apolipoprotein E (APOE) epsilon4 allele show significantly higher risk of Alzheimer disease (AD).
- The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD.
- A significant statistical interaction between APOE and gender was shown (p = 0.04) in logistic regression analysis.
- For men, the presence of the APOE-epsilon4 allele was not associated with a statistically significant increased risk (OR = 1.6, 95% CI = 0.5-5.3).
- The analysis suggests that the presence of one or more APOE-epsilon4 allele confers a substantially greater risk of AD to women than to men.
Why it matters
This study found a statistical interaction between APOE genotype and gender, with women carrying an APOE epsilon4 allele having a substantially greater risk of Alzheimer's disease than men carrying the allele. This is about risk patterns and does not provide a treatment, cure, or prevention.
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Study details
- Study designlongitudinal study
- Participants195
- Effect sizeOR = 1.6
- Evidence strengthModerate
How this study scored 61/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer disease and associated disorders) |
| Journal's citation record | 1 / 4 | Alzheimer Disease & Associated Disorders: journal h-index 131 (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 | 1999 — older than 20 years, still counted |
| Sample size | 2 / 4 | 195 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 5 / 7 | Cited 185 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.4 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 3 / 6 | Cited 3.3× 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 | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Victor W. Henderson: h-index 79 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Southern California: institution h-index 1,521 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10609670) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 61 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Bretsky, P. M., Buckwalter, J. G., Seeman, T. E., Miller, C. A., Poirier, J., Schellenberg, G. D., et al. (1999). Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease. Alzheimer disease and associated disorders. https://doi.org/10.1097/00002093-199910000-00007
Vancouver
Bretsky PM, Buckwalter JG, Seeman TE, Miller CA, Poirier J, Schellenberg GD, et al. Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease. Alzheimer disease and associated disorders. 1999. doi:10.1097/00002093-199910000-00007. PMID: 10609670.
BibTeX
@article{bretsky1999-10609670,
author = {Bretsky, P. M. and Buckwalter, J. G. and Seeman, T. E. and Miller, C. A. and Poirier, J. and Schellenberg, G. D. and Finch, C. E. and Henderson, V. W.},
title = {{Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease}},
journal = {Alzheimer disease and associated disorders},
year = {1999},
doi = {10.1097/00002093-199910000-00007},
pmid = {10609670},
url = {https://doi.org/10.1097/00002093-199910000-00007}
}
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