Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Elizabeth H. Corder, Ann M. Saunders, Warren J. Strittmatter, D. E. Schmechel, Perry C. Gaskell, Gary W. Small, Allen D. Roses, J. L. Haines et al.. Science, 1993-08-13
Topic: Amyloid, tau and blood-test diagnosis
The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
Key findings
- The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD).
Why it matters
In 42 families with late onset Alzheimer's disease, risk for the disease increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles. The authors conclude that APOE-epsilon 4 gene dose is a major risk factor for late onset Alzheimer's disease, and in these families homozygosity was virtually sufficient to cause the disease by age 80.
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Study details
- Evidence strengthLow
How this study scored 63/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Science) |
| Journal's citation record | 4 / 4 | Science: journal h-index 1,754 (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 | 1 / 5 | 1993 — older than 20 years, still counted |
| 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 | 7 / 7 | Cited 9,472 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 270.6 citations a year over 35 year(s) since 1993 |
| Impact for its field and year | 6 / 6 | Cited 127.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 6 / 6 | Cited by 438 other studies in this library |
| Still being cited | 4 / 4 | Cited 1,026 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 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8346443) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
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Read the original
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., et al. (1993). Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families. Science. https://doi.org/10.1126/science.8346443
Vancouver
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families. Science. 1993. doi:10.1126/science.8346443. PMID: 8346443.
BibTeX
@article{corder1993-8346443,
author = {Corder, Elizabeth H. and Saunders, Ann M. and Strittmatter, Warren J. and Schmechel, D. E. and Gaskell, Perry C. and Small, Gary W. and Roses, Allen D. and Haines, J. L. and others},
title = {{Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families}},
journal = {Science},
year = {1993},
doi = {10.1126/science.8346443},
pmid = {8346443},
url = {https://doi.org/10.1126/science.8346443}
}
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