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ATP-binding cassette transporter A1: From metabolism to neurodegeneration
Open accessAbstract
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE). ABCA1 is an essential regulator of high density lipoproteins (HDL) and reverse cholesterol transport - a role that determines its importance for atherosclerosis. Over the last 10 years studies have provided convincing evidence that ABCA1, via its control of apoE lipidation, also has a role in Alzheimer's disease (AD). A series of reports have revealed a significant impact of ABCA1 on Aβ deposition and clearance in AD model mice, as well as an association of common and rare ABCA1 gene variants with the risk for AD. Since APOE is the major genetic risk factor for late onset AD, the regulation of apoE level or its functionality by ABCA1 may prove significant for AD pathogenesis. ABCA1 is transcriptionally regulated by Liver X Receptors (LXR) and Retinoic X Receptors (RXR) which provides a starting point for drug discovery and development of synthetic LXR and RXR agonists for treatment of metabolic and neurodegenerative disorders. This review summarizes the recent results of research on ABCA1, particularly relevant to atherosclerosis and AD.
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“In addition to its role in lipid transport, ABCA1 also indirectly facilitates amyloid β clearance through ApoE lipidation in brain [6].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [6]
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“Deletion of ABCA1 gene increases amyloid β accumulation, whereas its overexpression prevents amyloid β aggregation in amyloid mouse models [6].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [6]
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“Agonists of these nuclear receptors increased the levels of ABCA1 and decreased amyloid β accumulation in APP mouse models [6].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [6]
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“ATP-binding cassette transporter A1 (ABCA1) is a major cholesterol transporter that transfers cellular cholesterol onto lipid-poor apolipoproteins and regulates ApoE lipidation in the brain (Koldamova et al., 2014).”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Koldamova et al., 2014
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“Previous animal studies demonstrated that improvement of ApoE lipidation inhibits amyloid deposition in APP mouse models.”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [6]
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InfluentialReversal of apoE4-driven brain pathology and behavioral deficits by bexarotene
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Association of ATP-Binding Cassette Transporter Variants With the Risk of Alzheimer‘s Disease
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Comprehensive Review on Alzheimer’s Disease: Causes and Treatment
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“ABCA1, via its control of ApoE lipidation, has a role in Alzheimer’s disease (AD) and has impact on Aβ deposition and clearance in ADmodel mice [234].”
BackgroundApolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease
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BackgroundApoE Lipidation as a therapeutic target in Alzheimer’s disease
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Metadata
- Authors
- Koldamova, R., Fitz, N. F., & Lefterov, I.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Koldamova, Radosveta
- Lefterov, Iliya
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 72
- Pages
- 13-21
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC4302328
- OpenAlex
- W2013375919
- Cited by
- 144
- References
- 146
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 6 · 2023: 18 · 2022: 12 · 2021: 12 · 2020: 6 · 2019: 12 · 2018: 11 · 2017: 11 · 2016: 10 · 2015: 11 · 2014: 2
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (R01AG037481, R01AG037919, R21ES021243, K01AG044490)
- DOD (W81XWH-13-1-0384)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- ABCA1, ABC transporters, Alzheimer's disease, atherosclerosis, reverse cholesterol transport, high-density lipoprotein, apolipoprotein E, apolipoprotein A-I, amyloid-beta clearance, liver X receptor, retinoid X receptor, LXR agonists, RXR agonists, cholesterol efflux, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Brain, Disease Models, Animal, Humans, Risk Factors, Tangier Disease, Amyloid beta-Peptides, Atherosclerosis, Mice, ATP Binding Cassette Transporter 1
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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