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High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease
Pottier C, Hannequin D, Coutant S, Rovelet-Lecrux A, Wallon D, Rousseau S, Legallic S, Paquet C et al.. Molecular psychiatry, 2012-04-03
Topic: Amyloid, tau and blood-test diagnosis
Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample.
Key findings
- These mutations were not retrieved in 1500 controls of same ethnic origin.
- In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample.
- Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect.
- SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production.
Why it matters
In people with autosomal dominant early-onset Alzheimer's disease without mutations in known genes, several potentially pathogenic SORL1 mutations were found and were absent from controls. This genetic finding links SORL1 to a rare inherited form of the disease but does not by itself provide a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people 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 50 of the 96 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | 3 / 4 | Molecular Psychiatry: journal h-index 318 (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 | 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 | 6 / 7 | Cited 307 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.2 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 12.7× 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 50 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22472873) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 50 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 50 of the 96 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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Read the original
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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
Pottier, C., Hannequin, D., Coutant, S., Rovelet-Lecrux, A., Wallon, D., Rousseau, S., et al. (2012). High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease. Molecular psychiatry. https://doi.org/10.1038/mp.2012.15
Vancouver
Pottier C, Hannequin D, Coutant S, Rovelet-Lecrux A, Wallon D, Rousseau S, et al. High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease. Molecular psychiatry. 2012. doi:10.1038/mp.2012.15. PMID: 22472873.
BibTeX
@article{pottier2012-22472873,
author = {Pottier, C. and Hannequin, D. and Coutant, S. and Rovelet-Lecrux, A. and Wallon, D. and Rousseau, S. and Legallic, S. and Paquet, C. and others},
title = {{High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease}},
journal = {Molecular psychiatry},
year = {2012},
doi = {10.1038/mp.2012.15},
pmid = {22472873},
url = {https://doi.org/10.1038/mp.2012.15}
}
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