The association between a polygenic Alzheimer score and cortical thickness in clinically normal subjects
Sabuncu MR, Buckner RL, Smoller JW, Lee PH, Fischl B, Sperling RA, Alzheimer's Disease Neuroimaging Initiative.. Cerebral cortex (New York, N.Y. : 1991), 2011-12-13
Topic: Amyloid, tau and blood-test diagnosis
Late-onset Alzheimer's disease (AD) is 50-70% heritable with complex genetic underpinnings. In addition to Apoliprotein E (APOE) ε4, the major genetic risk factor, recent genome-wide association studies (GWAS) have identified a growing list of sequence variations associated with the disease. Building on a prior large-scale AD GWAS, we used a recently developed analytic method to compute a polygenic score that involves up to 26 independent common sequence variants and is associated with AD dementia, above and beyond APOE. We then examined the associations between the polygenic score and the magnetic resonance imaging-derived thickness measurements across AD-vulnerable cortex in clinically normal (CN) human subjects (N = 104). AD-specific cortical thickness was correlated with the polygenic risk score, even after controlling for APOE genotype and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ(1-42)). Furthermore, the association remained significant in CN subjects with levels of CSF Aβ(1-)(42) in the normal range and in APOE ε3 homozygotes. The observation that genetic risk variants are associated with thickness across AD-vulnerable regions of interest in CN older individuals, suggests that the combination of polygenic risk profile, neuroimaging, and CSF biomarkers may hold synergistic potential to aid in the prediction of future cognitive decline.
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APA 7th
Sabuncu, M. R., Buckner, R. L., Smoller, J. W., Lee, P. H., Fischl, B., Sperling, R. A., et al. (2012). The association between a polygenic Alzheimer score and cortical thickness in clinically normal subjects. Cerebral cortex (New York, N.Y. : 1991). https://doi.org/10.1093/cercor/bhr348
Vancouver
Sabuncu MR, Buckner RL, Smoller JW, Lee PH, Fischl B, Sperling RA, et al. The association between a polygenic Alzheimer score and cortical thickness in clinically normal subjects. Cerebral cortex (New York, N.Y. : 1991). 2012. doi:10.1093/cercor/bhr348. PMID: 22169231.
BibTeX
@article{sabuncu2012-22169231,
author = {Sabuncu, M. R. and Buckner, R. L. and Smoller, J. W. and Lee, P. H. and Fischl, B. and Sperling, R. A. and {Alzheimer's Disease Neuroimaging Initiative}},
title = {{The association between a polygenic Alzheimer score and cortical thickness in clinically normal subjects}},
journal = {Cerebral cortex (New York, N.Y. : 1991)},
year = {2012},
doi = {10.1093/cercor/bhr348},
pmid = {22169231},
url = {https://doi.org/10.1093/cercor/bhr348}
}
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.
Key findings
- In addition to Apoliprotein E (APOE) ε4, the major genetic risk factor, recent genome-wide association studies (GWAS) have identified a growing list of sequence variations associated with the disease.
- Building on a prior large-scale AD GWAS, we used a recently developed analytic method to compute a polygenic score that involves up to 26 independent common sequence variants and is associated with AD dementia, above and beyond APOE.
- Furthermore, the association remained significant in CN subjects with levels of CSF Aβ(1-)(42) in the normal range and in APOE ε3 homozygotes.
- The observation that genetic risk variants are associated with thickness across AD-vulnerable regions of interest in CN older individuals, suggests that the combination of polygenic risk profile, neuroimaging, and CSF biomarkers may hold synergistic potential to aid in the prediction of future cognitive decline.
Why it matters
In clinically normal older people, a polygenic score based on up to 26 common genetic variants was associated with thinner cortex in Alzheimer's-vulnerable regions, even after accounting for APOE genotype and CSF amyloid-beta1-42. This suggests genetic risk, imaging, and CSF markers might together help predict future cognitive decline, but it does not provide a treatment or prevention.
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Study details
- Participants104
- Evidence strengthLow
How this study scored 52/100
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 (Cerebral cortex (New York, N.Y. : 1991)) |
| Journal's citation record | 3 / 4 | Cerebral Cortex: journal h-index 345 (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 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 104 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 133 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.3 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 2 / 6 | Cited 2.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Reisa Anne Sperling: h-index 157 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22169231) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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