Topic: Amyloid, tau and blood-test diagnosis
Although it is clear that apoE plays an important role in the genetics of late-onset Alzheimer disease (AD), evidence exists that additional genes may play a role in AD, and estimates of the total contribution of apoE to the variance in onset of AD vary widely. Unfortunately, little information is available on the number and contribution of additional genes. We estimated the number of additional quantitative-trait loci and their contribution to the variance in age at onset of AD, as well as the contribution of apoE and sex, in an oligogenic segregation analysis of 75 families (742 individuals) ascertained for members with late-onset AD. We found evidence that four additional loci make a contribution to the variance in age at onset of late-onset AD that is similar to or greater in magnitude than that made by apoE, with one locus making a contribution several times greater than that of apoE. Additionally, we confirmed previous findings of a dose effect for the apoE varepsilon4 allele, a protective effect for the varepsilon2 allele, evidence for allelic interactions at the apoE locus, and a small protective effect for males. Furthermore, although we estimate that the apoE genotype can make a difference of </=17 years in age at onset of AD, our estimate of the contribution of apoE (7%-9%) to total variation in onset of AD is somewhat smaller than that which has previously been reported. Our results suggest that several genes that have not yet been localized may play a larger role than does apoE in late-onset AD.
Key findings
- We found evidence that four additional loci make a contribution to the variance in age at onset of late-onset AD that is similar to or greater in magnitude than that made by apoE, with one locus making a contribution several times greater than that of apoE.
- Our results suggest that several genes that have not yet been localized may play a larger role than does apoE in late-onset AD.
Why it matters
This segregation analysis of families with late-onset Alzheimer disease estimated that four additional loci contribute to variation in age at onset, with contributions similar to or greater than that of apoE. The results suggest several not-yet-localized genes may play a larger role than apoE, but no treatment or cure is offered.
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Study details
- Participants742
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (American journal of human genetics) |
| Journal's citation record | 3 / 4 | The American Journal of Human Genetics: journal h-index 385 (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 | 2000 — older than 20 years, still counted |
| Sample size | 2 / 4 | 742 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 | 5 / 7 | Cited 296 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.6 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 4 / 6 | Cited 12.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ellen M. Wijsman: h-index 70 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10631151) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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 7 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
Daw, E. W., Payami, H., Nemens, E. J., Nochlin, D., Bird, T. D., Schellenberg, G. D., et al. (2000). The number of trait loci in late-onset Alzheimer disease. American journal of human genetics. https://doi.org/10.1086/302710
Vancouver
Daw EW, Payami H, Nemens EJ, Nochlin D, Bird TD, Schellenberg GD, et al. The number of trait loci in late-onset Alzheimer disease. American journal of human genetics. 2000. doi:10.1086/302710. PMID: 10631151.
BibTeX
@article{daw2000-10631151,
author = {Daw, E. W. and Payami, H. and Nemens, E. J. and Nochlin, D. and Bird, T. D. and Schellenberg, G. D. and Wijsman, E. M.},
title = {{The number of trait loci in late-onset Alzheimer disease}},
journal = {American journal of human genetics},
year = {2000},
doi = {10.1086/302710},
pmid = {10631151},
url = {https://doi.org/10.1086/302710}
}
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