ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing
Satoh K, Abe-Dohmae S, Yokoyama S, St George-Hyslop P, Fraser PE.. The Journal of biological chemistry, 2015-08-10
Topic: Amyloid, tau and blood-test diagnosis
The ATP-binding cassette transporter A7 (ABCA7) has been identified as a susceptibility factor of late onset Alzheimer disease in genome-wide association studies. ABCA7 has been shown to mediate phagocytosis and affect membrane trafficking. The current study examined the impact of ABCA7 loss of function on amyloid precursor protein (APP) processing and generation of amyloid-β (Aβ). Suppression of endogenous ABCA7 in several different cell lines resulted in increased β-secretase cleavage and elevated Aβ. ABCA7 knock-out mice displayed an increased production of endogenous murine amyloid Aβ42 species. Crossing ABCA7-deficient animals to an APP transgenic model resulted in significant increases in the soluble Aβ as compared with mice expressing normal levels of ABCA7. Only modest changes in the amount of insoluble Aβ and amyloid plaque densities were observed once the amyloid pathology was well developed, whereas Aβ deposition was enhanced in younger animals. In vitro studies indicated a more rapid endocytosis of APP in ABCA7 knock-out cells that is mechanistically consistent with the increased Aβ production. These in vitro and in vivo findings indicate a direct role of ABCA7 in amyloid processing that may be associated with its primary biological function to regulate endocytic pathways. Several potential loss-of-function ABCA7 mutations and deletions linked to Alzheimer disease that in some instances have a greater impact than apoE allelic variants have recently been identified. A reduction in ABCA7 expression or loss of function would be predicted to increase amyloid production and that may be a contributing factor in the associated Alzheimer disease susceptibility.
Key findings
- Crossing ABCA7-deficient animals to an APP transgenic model resulted in significant increases in the soluble Aβ as compared with mice expressing normal levels of ABCA7.
- These in vitro and in vivo findings indicate a direct role of ABCA7 in amyloid processing that may be associated with its primary biological function to regulate endocytic pathways.
Why it matters
In cell and mouse studies, loss of the ABCA7 gene increased beta-secretase cleavage and amyloid-beta production, and crossing ABCA7-deficient mice with an Alzheimer's mouse model increased soluble amyloid-beta. This laboratory work indicates a role for ABCA7 in amyloid processing but does not establish a treatment or prevention for people.
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Study details
- Evidence strengthLow
How this study scored 47/100
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 (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 5 / 7 | Cited 129 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.9 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 8.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 30 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Paul E. Fraser: h-index 30 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26260791) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. Check the citation against the original before you use it.
APA 7th
Satoh, K., Abe-Dohmae, S., Yokoyama, S., St George-Hyslop, P., & Fraser, P. E. (2015). ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m115.655076
Vancouver
Satoh K, Abe-Dohmae S, Yokoyama S, St George-Hyslop P, Fraser PE. ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing. The Journal of biological chemistry. 2015. doi:10.1074/jbc.m115.655076. PMID: 26260791.
BibTeX
@article{satoh2015-26260791,
author = {Satoh, K. and Abe-Dohmae, S. and Yokoyama, S. and St George-Hyslop, P. and Fraser, P. E.},
title = {{ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing}},
journal = {The Journal of biological chemistry},
year = {2015},
doi = {10.1074/jbc.m115.655076},
pmid = {26260791},
url = {https://doi.org/10.1074/jbc.m115.655076}
}
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