Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice
Koldamova R, Staufenbiel M, Lefterov I.. The Journal of biological chemistry, 2005-10-05
Topic: Brain proteins, microglia and lab models
ABCA1 (ATP-binding cassette transporter A1) is a major regulator of cholesterol efflux and high density lipoprotein (HDL) metabolism. Mutations in human ABCA1 cause severe HDL deficiencies characterized by the virtual absence of apoA-I and HDL and prevalent atherosclerosis. Recently, it has been reported that the lack of ABCA1 causes a significant reduction of apoE protein level in the brain of ABCA1 knock-out (ABCA1-/-) mice. ApoE isoforms strongly affect Alzheimer disease (AD) pathology and risk. To determine further the effect of ABCA1 on amyloid deposition, we used APP23 transgenic mice in which the human familial Swedish AD mutant is expressed only in neurons. We demonstrated that the targeted disruption of ABCA1 increases amyloid deposition in APP23 mice, and the effect is manifested by an increased level of Abeta immunoreactivity, as well as thioflavine S-positive plaques in brain parenchyma. We found that the lack of ABCA1 also considerably increased the level of cerebral amyloid angiopathy and exacerbated cerebral amyloid angiopathy-related microhemorrhage in APP23/ABCA1-/- mice. Remarkably, the elevation in parenchymal and vascular amyloid in APP23/ABCA1-/- mice was accompanied by a dramatic decrease in the level of soluble brain apoE, although insoluble apoE was not changed. The elevation of insoluble Abeta fraction in old APP23/ABCA1-/- mice, accompanied by a lack of changes in APP processing and soluble beta-amyloid in young APP23/ABCA1-/- animals, supports the conclusion that the ABCA1 deficiency increases amyloid deposition. These results suggest that ABCA1 plays a role in the pathogenesis of parenchymal and cerebrovascular amyloid pathology and thus may be considered a therapeutic target in AD.
Key findings
- Recently, it has been reported that the lack of ABCA1 causes a significant reduction of apoE protein level in the brain of ABCA1 knock-out (ABCA1-/-) mice.
- We demonstrated that the targeted disruption of ABCA1 increases amyloid deposition in APP23 mice, and the effect is manifested by an increased level of Abeta immunoreactivity, as well as thioflavine S-positive plaques in brain parenchyma.
- We found that the lack of ABCA1 also considerably increased the level of cerebral amyloid angiopathy and exacerbated cerebral amyloid angiopathy-related microhemorrhage in APP23/ABCA1-/- mice.
- These results suggest that ABCA1 plays a role in the pathogenesis of parenchymal and cerebrovascular amyloid pathology and thus may be considered a therapeutic target in AD.
Why it matters
In this mouse study, targeted disruption of ABCA1 increased amyloid deposition in APP23 mice, increased cerebral amyloid angiopathy and related microhemorrhage, and dramatically decreased the level of soluble brain apoE. This is animal work describing how loss of ABCA1 affects amyloid, and it does not show that any treatment, cure, or prevention works in 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 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 | 2005 — older than 20 years, still counted |
| 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 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 351 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.3 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 9.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 20 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 Iliya M. Lefterov: h-index 34 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pittsburgh: institution h-index 1,470 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16207713) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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APA 7th
Koldamova, R., Staufenbiel, M., & Lefterov, I. (2005). Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m504513200
Vancouver
Koldamova R, Staufenbiel M, Lefterov I. Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m504513200. PMID: 16207713.
BibTeX
@article{koldamova2005-16207713,
author = {Koldamova, R. and Staufenbiel, M. and Lefterov, I.},
title = {{Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice}},
journal = {The Journal of biological chemistry},
year = {2005},
doi = {10.1074/jbc.m504513200},
pmid = {16207713},
url = {https://doi.org/10.1074/jbc.m504513200}
}
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