Topic: Amyloid, tau and blood-test diagnosis
It was one of the genes most strongly associated with risk of Alzheimer's disease in a Belgian cohort. Using targeted resequencing, we investigated ABCA7 in this cohort with the aim to directly detect rare and common variations in this gene associated with Alzheimer's disease pathogenesis. Findings An intronic low-frequency variant rs78117248 (minor allele frequency 3·8% in 58 patients with Alzheimer's disease and in controls 1·8% in 28 controls) showed strongest association with Alzheimer's disease (odds ratio 2·07, 95% CI 1·31-3·27; p=0·0016), and remained significant after conditioning for the GWAS top single nucleotide polymorphisms rs3764650, rs4147929, and rs3752246 (2·00, 1·22-3·26; p=0·006). We identified an increased frequency of predicted loss-of-function mutations in the patients compared with the controls (relative risk 4·03, 95% CI 1·75-9·29; p=0·0002). Expression of ABCA7 was reduced in the two carriers of loss-of-function mutations found only in patients with Alzheimer's disease (Glu709fs and Trp1214*) compared with four non-carrier controls (relative expression 0·45, 95% CI 0·25-0·84; p=0·002) and in lymphoblast cell lines from three carriers of Glu709fs compared with those from two non-carrier controls. Interpretation We propose that a low-frequency variant can explain the association between ABCA7 and Alzheimer's disease, and the evidence of loss-of-function mutations in this risk gene suggests that partial loss-of-function of ABCA7 could be a potential pathogenetic mechanism of Alzheimer's disease.
Key findings
- It was one of the genes most strongly associated with risk of Alzheimer's disease in a Belgian cohort.
- Using targeted resequencing, we investigated ABCA7 in this cohort with the aim to directly detect rare and common variations in this gene associated with Alzheimer's disease pathogenesis.
- Findings An intronic low-frequency variant rs78117248 (minor allele frequency 3·8% in 58 patients with Alzheimer's disease and in controls 1·8% in 28 controls) showed strongest association with Alzheimer's disease (odds ratio 2·07, 95% CI 1·31-3·27; p=0·0016), and remained significant after conditioning for the GWAS top single nucleotide polymorphisms rs3764650, rs4147929, and rs3752246 (2·00, 1·22-3·26; p=0·006).
- We identified an increased frequency of predicted loss-of-function mutations in the patients compared with the controls (relative risk 4·03, 95% CI 1·75-9·29; p=0·0002).
- Expression of ABCA7 was reduced in the two carriers of loss-of-function mutations found only in patients with Alzheimer's disease (Glu709fs and Trp1214*) compared with four non-carrier controls (relative expression 0·45, 95% CI 0·25-0·84; p=0·002) and in lymphoblast cell lines from three carriers of Glu709fs compared with those from two non-carrier controls.
Why it matters
In a Belgian cohort, a low-frequency ABCA7 variant and predicted loss-of-function mutations in ABCA7 were more common in Alzheimer's disease patients than controls, and ABCA7 expression was reduced in carriers of these mutations. This identifies a genetic risk factor for Alzheimer's disease but does not show that targeting ABCA7 treats, cures, or prevents the disease.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Participants183
- Evidence strengthModerate
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (The Lancet. Neurology) |
| Journal's citation record | 3 / 4 | The Lancet Neurology: journal h-index 457 (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 | 3 / 5 | Rated “moderate” 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 | 2 / 4 | 183 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 154 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.8 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 13.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Kristel Sleegers: h-index 81 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | KU Leuven: institution h-index 1,386 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26141617) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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
Cuyvers, E., De Roeck, A., Van den Bossche, T., Van Cauwenberghe, C., Bettens, K., Vermeulen, S., et al. (2015). Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study. The Lancet. Neurology. https://doi.org/10.1016/s1474-4422(15)00133-7
Vancouver
Cuyvers E, De Roeck A, Van den Bossche T, Van Cauwenberghe C, Bettens K, Vermeulen S, et al. Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study. The Lancet. Neurology. 2015. doi:10.1016/s1474-4422(15)00133-7. PMID: 26141617.
BibTeX
@article{cuyvers2015-26141617,
author = {Cuyvers, E. and De Roeck, A. and Van den Bossche, T. and Van Cauwenberghe, C. and Bettens, K. and Vermeulen, S. and Mattheijssens, M. and Peeters, K. and others},
title = {{Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study}},
journal = {The Lancet. Neurology},
year = {2015},
doi = {10.1016/s1474-4422(15)00133-7},
pmid = {26141617},
url = {https://doi.org/10.1016/s1474-4422(15)00133-7}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 13.
Later studies that cite this one
13 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Genetics
Also tagged “amyloid-beta”
1,339 studies in the library carry the topic tag “amyloid-beta”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.