Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease
Carrasquillo MM, Crook JE, Pedraza O, Thomas CS, Pankratz VS, Allen M, Nguyen T, Malphrus KG et al.. Neurobiology of aging, 2014-08-04
Topic: Amyloid, tau and blood-test diagnosis
We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease.
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APA 7th
Carrasquillo, M. M., Crook, J. E., Pedraza, O., Thomas, C. S., Pankratz, V. S., Allen, M., et al. (2015). Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2014.07.042
Vancouver
Carrasquillo MM, Crook JE, Pedraza O, Thomas CS, Pankratz VS, Allen M, et al. Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease. Neurobiology of aging. 2015. doi:10.1016/j.neurobiolaging.2014.07.042. PMID: 25189118.
BibTeX
@article{carrasquillo2015-25189118,
author = {Carrasquillo, M. M. and Crook, J. E. and Pedraza, O. and Thomas, C. S. and Pankratz, V. S. and Allen, M. and Nguyen, T. and Malphrus, K. G. and others},
title = {{Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease}},
journal = {Neurobiology of aging},
year = {2015},
doi = {10.1016/j.neurobiolaging.2014.07.042},
pmid = {25189118},
url = {https://doi.org/10.1016/j.neurobiolaging.2014.07.042}
}
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Key findings
- APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory.
- CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD.
- MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory.
- ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD.
- Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD.
Why it matters
Of nine late-onset Alzheimer risk variants tested in over 2000 older adults, only APOE-e4 was strongly linked to worse memory and progression to mild cognitive impairment or Alzheimer disease. The collective effect of the other variants appeared limited, and no treatment was tested.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (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 | 2015 — 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 | 4 / 7 | Cited 97 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 3 / 6 | Cited 7.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Nilüfer Ertekin‐Taner: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25189118) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
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Read the original
- DOI: 10.1016/j.neurobiolaging.2014.07.042
- PubMed: 25189118
- 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).
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