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Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families
Cruchaga C, Haller G, Chakraverty S, Mayo K, Vallania FL, Mitra RD, Faber K, Williamson J et al.. PloS one, 2012-02-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD). Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs.
What this study adds
Evidence grade: Low
Screening of 439 probands from late-onset Alzheimer's families found rare variants in APP, PSEN1, and PSEN2 in some individuals. Reported effect size: 13.7%; OR = 2.21; OR = 2.19.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Cruchaga, C., Haller, G., Chakraverty, S., Mayo, K., Vallania, F. L., Mitra, R. D., et al. (2012). Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PloS one. https://doi.org/10.1371/journal.pone.0031039
Vancouver
Cruchaga C, Haller G, Chakraverty S, Mayo K, Vallania FL, Mitra RD, et al. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PloS one. 2012. doi:10.1371/journal.pone.0031039. PMID: 22312439.
BibTeX
@article{cruchaga2012-22312439,
author = {Cruchaga, C. and Haller, G. and Chakraverty, S. and Mayo, K. and Vallania, F. L. and Mitra, R. D. and Faber, K. and Williamson, J. and others},
title = {{Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families}},
journal = {PloS one},
year = {2012},
doi = {10.1371/journal.pone.0031039},
pmid = {22312439},
url = {https://doi.org/10.1371/journal.pone.0031039}
}
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
- Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD).
- Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs.
- We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals.
- Sixty sequenced individuals (13.7%) carried a novel or pathogenic mutation.
Why it matters
Screening of 439 probands from late-onset Alzheimer's families found rare variants in APP, PSEN1, and PSEN2 in some individuals. This identifies genetic risk factors but does not provide a treatment or cure.
Study details
- Effect size13.7%; OR = 2.21; OR = 2.19
- Evidence strengthLow
How this study scored 59/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PloS one) |
| Journal's citation record | 4 / 4 | PLoS ONE: journal h-index 594 (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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 322 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.1 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 18.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 3 / 4 | Cited 53 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Alison Goate: h-index 156 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22312439) |
| Free to read | 2 / 2 | Free to read |
| Total | 59 / 100 | — |
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