Lack of ABCA1 Considerably Decreases Brain ApoE Level and Increases Amyloid Deposition in APP23 Mice
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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 c…
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Deletion of Abca1 and Lxr genes decreased apoE levels but increased or had no effect on Aβ deposition.
“Interestingly, deletion of ATP-binding cassette, sub-family A1 (Abca1) and liver x receptor (Lxr) genes decreased apoE levels but increased or had no effect on Aβ deposition (Hirsch-Reinshagen et al.,2005; Koldamova et al., 2005; Wahrle et al., 2005; Zelcer et al., 2007).”
From Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis (2011) · cites this paper as Koldamova et al., 2005
ABCA1-mediated lipidation of apoE modulates amyloid plaque formation.
“In support of this possibility, it was recently demonstrated that ATP-binding cassette transporter A1 (ABCA1)-mediated lipidation of apoE modulates amyloid plaque formation (Hirsch-Reinshagen et al., 2005; Koldamova et al., 2005; Wahrle et al., 2005; Wahrle et al., 2008).”
From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as Koldamova et al., 2005
Knocking out Abca1 in amyloidosis mouse models increases the formation of Aβ peptides and amyloid plaque deposition.
“Interestingly, several studies have shown that knocking out Abca1 in amyloidosis mouse models increases the formation of Aβ peptides and amyloid plaque deposition. 11 , 12”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [11]
ABCA1 levels regulate Aβ deposition in vivo.
“Moreover, animal studies have demonstrated that ABCA1 levels regulate A deposition in vivo (Hirsch-Reinshagen et al., 2004;Wahrle et al., 2004Wahrle et al., , 2005Wahrle et al., , 2008;;Koldamova et al., 2005).”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Koldamova et al., 2005
ABCA1 overexpression or LXR/RXR agonist treatment decreases amyloid deposition in APP transgenic mouse models.
“ABCA1 overexpression or LXR/RXR agonist treatment decreased amyloid deposition [66-69].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [67]
ABCA1 gene ablation in mice decreases APOE lipidation and levels and increases Aβ accumulation in APP transgenic mouse models.
“ABCA1 gene ablation in mice decreased APOE lipidation and levels and increased Aβ accumulation in APP transgenic mouse models.”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [67]
Modulation of ABCA1 affects Aβ levels and amyloid accumulation in vivo.
“We and others demonstrated that modulation of ABCA1 affects Aβ levels and amyloid accumulation in vivo.”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Koldamova et al., 2005
Deletion of ABCA1 increases Aβ deposition in AD mouse models.
“Genetic studies with AD mouse models have demonstrated that the deletion of ABCA1 increases Aβ deposition, while overexpression of ABCA1 dramatically reduces Aβ deposition (Hirsch-Reinshagen et al., 2004; Koldamova et al., 2005; Wahrle et al., 2005; Wahrle et al., 2008; Wahrle et al., 2004).”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Koldamova et al., 2005
Overexpression of ABCA1 reduces Aβ deposition in AD mouse models.
“Genetic studies with AD mouse models have demonstrated that the deletion of ABCA1 increases Aβ deposition, while overexpression of ABCA1 dramatically reduces Aβ deposition (Hirsch-Reinshagen et al., 2004; Koldamova et al., 2005; Wahrle et al., 2005; Wahrle et al., 2008; Wahrle et al., 2004).”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Koldamova et al., 2005
ABCA1 deficiency leads to an increase in Aβ and amyloid deposition.
“ABCA1 deficiency leads to an increase in Aβ and amyloid deposition (Hirsch-Reinshagen et al., 2005; Koldamova et al., 2005; Wahrle et al., 2005)”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Koldamova et al., 2005
The amyloid load in APP transgenic mice deficient in ABCA1 does not change, or even increases, when ABCA1−/− mice are crossed to various APP transgenic models.
“The amyloid load in APP transgenic mice deficient in ABCA1 did not change, or even increased, when ABCA1−/− mice were crossed to various APP transgenic models [40-42].”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [41]
We did not explore the lipidation status of different APOE isoforms, which influences Aβ pathology.
“Additionally, we did not explore the lipidation status of different APOE isoforms, which influences Aβ pathology (Koldamova et al, 2005; Wahrle et al, 2005).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Koldamova et al, 2005
ABCA1 deletion did not have an effect on Aβ production.
“ABCA1 deletion did not have an effect on Aβ production (Koldamova et al., 2005; Wahrle et al., 2005), suggesting that the presence of poorly lipidated apoE somehow promotes the formation of amyloid fibrils.”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Koldamova et al., 2005
ABCA1 deficiency leads to an increase in both Aβ and amyloid load in the brains of three different transgenic APP mouse models.
“However, three independent studies demonstrated that ABCA1 deficiency leads to an increase in both Aβ and amyloid load in the brains of three different transgenic APP mouse models (Hirsch-Reinshagen et al., 2005; Koldamova et al., 2005; Wahrle et al., 2005).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Koldamova et al., 2005
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References 79 · Cited by 350
- Authors
- Koldamova, R., Staufenbiel, M., & Lefterov, I.
- Affiliations
- University of Pittsburgh (US)
- Novartis Institutes for BioMedical Research (CH)
- Corresponding author
- Koldamova, Radosveta
- Lefterov, Iliya
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 280
- Issue
- 52
- Pages
- 43224-43235
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1989076425
- Cited by
- 350
- References
- 79
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 12 · 2023: 12 · 2022: 20 · 2021: 9 · 2020: 10 · 2019: 17 · 2018: 12 · 2017: 16 · 2016: 16 · 2015: 20 · 2014: 28 · 2013: 21 · 2012: 26
- FWCI
- 11.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R21AG023662, AG023662, AG023304, R03AG023304)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- ABCA1, apolipoprotein E, amyloid deposition, Alzheimer's disease, APP23 transgenic mice, cerebral amyloid angiopathy, amyloid-beta, amyloid plaques, microhemorrhages, cholesterol efflux, HDL metabolism, APOE isoforms, therapeutic target
- MeSH terms
- Alzheimer Disease, Amyloid, Animals, Apolipoproteins E, Brain, Humans, Immunohistochemistry, Lipoproteins, HDL, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Mutation, Thiazoles, Time Factors, Blotting, Western, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Mice, Knockout, ATP-Binding Cassette Transporters, Protein Isoforms, Atherosclerosis, Lipid Metabolism, Mice, Benzothiazoles, ATP Binding Cassette Transporter 1
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