Topic: Amyloid, tau and blood-test diagnosis
Background Apolipoprotein E (APOE) is the most statistically significant genetic risk factor for late-onset Alzheimer disease (LOAD). The linkage disequilibrium pattern around the APOE gene has made it difficult to determine whether all the association signal is derived from APOE or whether there is an independent signal from a nearby gene. Objective To attempt to replicate a recently reported association of APOE 3-TOMM40 haplotypes with risk and age at onset. Design We used standard techniques to genotype several polymorphisms in the APOE-TOMM40 region in a large case-control series, in a series with cerebrospinal fluid biomarker data, and in brain tissue. Setting Alzheimer's Disease Research Center. Participants Research volunteers who were cognitively normal or had Alzheimer disease. Main outcome measures Disease status and age at onset. Results We did not replicate the previously reported association of the polyT polymorphism (rs10524523) with risk and age at onset. We found a significant association between rs10524523 and risk of LOAD in APOE 33 homozygotes but in the opposite direction as the previously reported association (the very long allele was underrepresented in cases vs controls in this study (P = .004]). We found no association between rs10524523 and cerebrospinal fluid tau or β-amyloid 42 levels or TOMM40 or APOE gene expression. Conclusions Although we did not replicate the earlier association between the APOE 3-TOMM40 haplotypes and age at onset, we observed that the polyT polymorphism is associated with risk of LOAD in APOE 33 homozygotes in a large case-control series but in the opposite direction as in the previous study.
Key findings
- Background Apolipoprotein E (APOE) is the most statistically significant genetic risk factor for late-onset Alzheimer disease (LOAD).
- Results We did not replicate the previously reported association of the polyT polymorphism (rs10524523) with risk and age at onset.
- We found a significant association between rs10524523 and risk of LOAD in APOE 33 homozygotes but in the opposite direction as the previously reported association (the very long allele was underrepresented in cases vs controls in this study (P = .004]).
- We found no association between rs10524523 and cerebrospinal fluid tau or β-amyloid 42 levels or TOMM40 or APOE gene expression.
- Conclusions Although we did not replicate the earlier association between the APOE 3-TOMM40 haplotypes and age at onset, we observed that the polyT polymorphism is associated with risk of LOAD in APOE 33 homozygotes in a large case-control series but in the opposite direction as in the previous study.
Why it matters
This study did not replicate a previously reported link between a TOMM40 polyT variant and Alzheimer risk or age at onset. It found a link in APOE 33 homozygotes but in the opposite direction to the earlier report, and no link to CSF tau or amyloid-beta42.
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Study details
- Study designcase-control study
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 6 / 12 | A case-control study |
| 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 | 2011 — within 20 year(s) of the newest study here |
| 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 | 5 / 7 | Cited 104 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.1 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 8.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Carlos C Cruchaga: h-index 102 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21825236) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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Read the original
- DOI: 10.1001/archneurol.2011.155
- PubMed: 21825236
- Original source →
- Free full text: PubMed Central →
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'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
Cruchaga, C., Nowotny, P., Kauwe, J. S., Ridge, P. G., Mayo, K., Bertelsen, S., et al. (2011). Association and expression analyses with single-nucleotide polymorphisms in TOMM40 in Alzheimer disease. Archives of neurology. https://doi.org/10.1001/archneurol.2011.155
Vancouver
Cruchaga C, Nowotny P, Kauwe JS, Ridge PG, Mayo K, Bertelsen S, et al. Association and expression analyses with single-nucleotide polymorphisms in TOMM40 in Alzheimer disease. Archives of neurology. 2011. doi:10.1001/archneurol.2011.155. PMID: 21825236.
BibTeX
@article{cruchaga2011-21825236,
author = {Cruchaga, C. and Nowotny, P. and Kauwe, J. S. and Ridge, P. G. and Mayo, K. and Bertelsen, S. and Hinrichs, A. and Fagan, A. M. and others},
title = {{Association and expression analyses with single-nucleotide polymorphisms in TOMM40 in Alzheimer disease}},
journal = {Archives of neurology},
year = {2011},
doi = {10.1001/archneurol.2011.155},
pmid = {21825236},
url = {https://doi.org/10.1001/archneurol.2011.155}
}
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