Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory
Barral S, Bird T, Goate A, Farlow MR, Diaz-Arrastia R, Bennett DA, Graff-Radford N, Boeve BF et al.. Neurology, 2012-04-25
Topic: Brain proteins, microglia and lab models
Objective Several genome-wide association studies (GWAS) have associated variants in late-onset Alzheimer disease (LOAD) susceptibility genes; however, these single nucleotide polymorphisms (SNPs) have very modest effects, suggesting that single SNP approaches may be inadequate to identify genetic risks. An alternative approach is the use of multilocus genotype patterns (MLGPs) that combine SNPs at different susceptibility genes. Methods Using data from 1,365 subjects in the National Institute on Aging Late-Onset Alzheimer's Disease Family Study, we conducted a family-based association study in which we tabulated MLGPs for SNPs at CR1, BIN1, CLU, PICALM, and APOE. We used generalized estimating equations to model episodic memory as the dependent endophenotype of LOAD and the MLGPs as predictors while adjusting for sex, age, and education. Results Several genotype patterns influenced episodic memory performance. A pattern that included PICALM and CLU was the strongest genotypic profile for lower memory performance (β = -0.32, SE = 0.19, p = 0.021). The effect was stronger after addition of APOE (p = 0.016). Two additional patterns involving PICALM, CR1, and APOE and another pattern involving PICALM, BIN1, and APOE were also associated with significantly poorer memory performance (β = -0.44, SE = 0.09, p = 0.009 and β = -0.29, SE = 0.07, p = 0.012) even after exclusion of patients with LOAD. We also identified genotype pattern involving variants in PICALM, CLU, and APOE as a predictor of better memory performance (β = 0.26, SE = 0.10, p = 0.010). Conclusions MLGPs provide an alternative analytical approach to predict an individual's genetic risk for episodic memory performance, a surrogate indicator of LOAD. Identifying genotypic patterns contributing to the decline of an individual's cognitive performance may be a critical step along the road to preclinical detection of Alzheimer disease.
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APA 7th
Barral, S., Bird, T., Goate, A., Farlow, M. R., Diaz-Arrastia, R., Bennett, D. A., et al. (2012). Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory. Neurology. https://doi.org/10.1212/wnl.0b013e3182553c48
Vancouver
Barral S, Bird T, Goate A, Farlow MR, Diaz-Arrastia R, Bennett DA, et al. Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory. Neurology. 2012. doi:10.1212/wnl.0b013e3182553c48. PMID: 22539578.
BibTeX
@article{barral2012-22539578,
author = {Barral, S. and Bird, T. and Goate, A. and Farlow, M. R. and Diaz-Arrastia, R. and Bennett, D. A. and Graff-Radford, N. and Boeve, B. F. and others},
title = {{Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory}},
journal = {Neurology},
year = {2012},
doi = {10.1212/wnl.0b013e3182553c48},
pmid = {22539578},
url = {https://doi.org/10.1212/wnl.0b013e3182553c48}
}
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.
Key findings
- Objective Several genome-wide association studies (GWAS) have associated variants in late-onset Alzheimer disease (LOAD) susceptibility genes; however, these single nucleotide polymorphisms (SNPs) have very modest effects, suggesting that single SNP approaches may be inadequate to identify genetic risks.
- Results Several genotype patterns influenced episodic memory performance.
- Two additional patterns involving PICALM, CR1, and APOE and another pattern involving PICALM, BIN1, and APOE were also associated with significantly poorer memory performance (β = -0.44, SE = 0.09, p = 0.009 and β = -0.29, SE = 0.07, p = 0.012) even after exclusion of patients with LOAD.
Why it matters
Combinations of gene variants, especially involving PICALM and CLU, were linked to poorer episodic memory in families with late-onset Alzheimer disease. This is a genetic association study of memory performance, not a test of treatment or prevention.
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Study details
- Participants1,365
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 52 of the 96 points we could judge it on, which is 54 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 3 / 4 | 1,365 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 101 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.3 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 3 / 6 | Cited 7.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 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 | OpenAlex's profile for last-listed author Ezinna Anosike holds only 1 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 24 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22539578) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 52 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 52 of the 96 points we could judge it on is 54 out of 100. |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0b013e3182553c48
- PubMed: 22539578
- 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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