Impact of Sample Selection on APOE ∈4 Allele Frequency: A Comparison of Two Alzheimer's Disease Samples
Abstract
Objective In a highly selected sample of unrelated Alzheimer's disease (AD) patients, we found that the APOE epsilon 4 allele frequency was higher than previously reported. Differing selection and ascertainment criteria may lead to these differences. To address this possibility, we compared the epsilon 4 allele frequency in two samples of AD patients selected from the same geographical area. Setting and participants Cases (n = 55) and controls (n = 99) from a research clinic-based sample were compared with subjects (n = 537) from a community-based AD patient sample. The samples consisted of unrelated cases who met NINCDS/ADRDA criteria for probable AD. Design and measurements Clinical characteristics and APOE genotype data were obtained from AD cases and controls from both samples. Results Frequency of APOE epsilon 4 allele in the research cases compared with the community cases (0.45 vs 0.36) was nearly significant. We compared demographic and clinical characteristics that might account for this difference and found that the research cases were younger, had an earlier age of onset, and had more advanced disease than the community cases. After onset age was controlled, there was no overall difference between epsilon 4 allele frequency of the two samples. Conclusions We found that the epsilon 4 allele frequency tended to be higher in the research AD sample compared the community-based sample. The two samples differed in several demographic and clinical characteristics. We conc…
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Most estimates of AD progression derive from convenience samples from dementia clinics or research centers, where there is substantial potential for survival bias and other distortions.
“Most estimates derive from convenience samples from dementia clinics or research centers where there is substantial potential for survival bias and other distortions.”
Clinic AD patients are more likely to be carriers of the APOE ε4 allele than population-ascertained AD cases.
“are more likely to be carriers of the Apolipoprotein E (APOE) ε4 allele,(6)”
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Self-citation
- Authors
- Tsuang, D., Kukull, W., Sheppard, L., Barnhart, R. L., Peskind, E., Edland, S. D., Schellenberg, G., Raskind, M., & Larson, E. B.
- Affiliations
- University of Washington (US)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Tsuang, Debby
- ORCID
- Venue
- Journal of the American Geriatrics Society
- Publisher
- Wiley
- Published
- 1996-06
- Volume
- 44
- Issue
- 6
- Pages
- 704-707
- ISSN
- 0002-8614 (ISSN-L)
- 1532-5415
- OpenAlex
- W2074222908
- Cited by
- 69
- References
- 3
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Geriatrics Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- University of Washington
- National Institute on Aging (P50 AG05136, U01-AG-06781, U01AG006781, R01AG07584, R01AG007584, P50AG005136)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- APOE ε4, allele frequency, Alzheimer's disease, sample selection bias, age of onset, disease severity, genetic association studies, NINCDS-ADRDA criteria
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Female, Gene Frequency, Genotype, Humans, Male, Washington, Selection Bias, Logistic Models, Case-Control Studies, Age of Onset, Apolipoprotein E4
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