The effects of ABCA1 on cholesterol efflux and Aβ levels in vitro and in vivo
Abstract
ABCA1 promotes cholesterol efflux from cells and is required for maintaining plasma cholesterol levels. Cholesterol homeostasis is important in the production of beta-amyloid (Abeta), a peptide that is overproduced in Alzheimer's disease (AD). Overexpression of ABCA1 can be achieved by stimulating Liver X Receptors (LXR), and changes in Abeta have been reported after LXR stimulation in vitro. To determine whether ABCA1 could alter endogenous Abeta levels, we used two different in vivo systems. We first examined the effects of an LXR agonist (TO-901317) on wild-type mice and found an increase in brain ABCA1 and apoE levels, which caused an increase in plasma cholesterol. This was accompanied by a decrease in brain Abeta levels. We then examined endogenous Abeta levels in ABCA1 knockout mice and found that, despite having no ABCA1, lowered brain apoE levels, and lowered plasma cholesterol, there was no change in Abeta levels. To assess these in vivo models in an in vitro system, we designed a model in which cholesterol transport via ABCA1 (or related transporters) was prevented. Switching off cholesterol efflux, even in the presence of TO-901317, caused no change in Abeta levels. However, when efflux capability was restored, TO-901317 reduced Abeta levels. These data show that promoting cholesterol efflux is a viable target for Abeta reducing strategies; however, knockout of cholesterol transporters is not sufficient to alter Abeta in vitro or in vivo.
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LXR agonist treatment alleviates AD-like pathology in mouse models of amyloidosis, possibly by inducing Abca1 expression.
“LXR agonist treatment alleviates AD-like pathology in mouse models of amyloidosis, possibly by inducing Abca1 expression (29, 43–48).”
From The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis (2015) · cites this paper as [43]
LXR agonists increase murine CNS apoE levels and decrease Aβ levels in APP transgenic mice.
“dosing of APP transgenic mice with LXR agonists, which increase murine CNS apoE levels, also decrease A levels (Koldamova et al., 2005;Burns et al., 2006;Riddell et al., 2007).”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Burns et al., 2006
Cites
Cirrito, J. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25247 · Cited by 660 · see citing works
Lund, E. G., Xie, C., Kotti, T., Turley, S. D., Dietschy, J. M., & Russell, D. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303415200 · Cited by 421 · see citing works
Koldamova, R. P., Lefterov, I. M., Staufenbiel, M., Wolfe, D., Huang, S., Glorioso, J. C., Walter, M., Roth, M. G., & Lazo, J. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411420200 · Cited by 279 · see citing works
Hirsch-Reinshagen, V., Maia, L. F., Burgess, B. L., Blain, J.-F., Naus, K. E., McIsaac, S. A., Parkinson, P. F., Chan, J. Y., Tansley, G. H., Hayden, M. R., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508781200 · Cited by 233 · see citing works
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Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425 · see citing works
ApoE Promotes the Proteolytic Degradation of Aβ
Jiang, Q., Lee, C. Y. D., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, N., Mann, K., Lamb, B., Willson, T. M., Collins, J. L., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.010 · Cited by 876 · see citing works
Liver X receptors in lipid signalling and membrane homeostasis
Wang, B., & Tontonoz, P. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0037-x · Cited by 722 · see citing works
Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33622 · Cited by 370 · see citing works
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 342 · see citing works
Riddell, D. R., Zhou, H., Comery, T. A., Kouranova, E., Lo, C. F., Warwick, H. K., Ring, R. H., Kirksey, Y., Aschmies, S., Xu, J., et al. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2007.01.011 · Cited by 244 · see citing works
Nuclear receptors as therapeutic targets for Alzheimer's disease
Mandrekar-Colucci, S., & Landreth, G. E. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.594043 · Cited by 126 · see citing works
The relationship between amyloid-beta and brain capillary endothelial cells in Alzheimer’s disease
Su, Q., Guo, J.-H., Zhang, Y.-L., Wang, J., & Zhang, Z.-N. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.335829 · Cited by 91 · see citing works
Lefterov, I., Bookout, A., Wang, Z., Staufenbiel, M., Mangelsdorf, D., & Koldamova, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-20 · Cited by 89 · see citing works
Fernández-de Frutos, M., Galán-Chilet, I., Goedeke, L., Kim, B., Pardo-Marqués, V., Pérez-García, A., Herrero, J. I., Fernández-Hernando, C., Kim, J., & Ramírez, C. M. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00170-19 · Cited by 82 · see citing works
Hirsch-Reinshagen, V., & Wellington, C. L. (2007) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32813aeabf · Cited by 61 · see citing works
Loane, D. J., Washington, P. M., Vardanian, L., Pocivavsek, A., Hoe, H.-S., Duff, K. E., Cernak, I., Rebeck, G. W., Faden, A. I., & Burns, M. P. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2010.1595 · Cited by 57 · see citing works
Self-citationAkram, A., Schmeidler, J., Katsel, P., Hof, P. R., & Haroutunian, V. (2010) · Brain Research · doi:10.1016/j.brainres.2010.01.006 · Cited by 50 · see citing works
Choi, J., Gao, J., Kim, J., Hong, C., Kim, J., & Tontonoz, P. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aad1904 · Cited by 49 · see citing works
- Authors
- Burns, M. P., Vardanian, L., Pajoohesh‐Ganji, A., Wang, L., Cooper, M., Harris, D. C., Duff, K., & Rebeck, G. W.
- Affiliations
- Georgetown University Medical Center (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Corresponding author
- Rebeck, G. William
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2006-06-19
- Volume
- 98
- Issue
- 3
- Pages
- 792-800
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1974761264
- Cited by
- 106
- References
- 4
- Citations by year
- 2025: 7 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 7
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG014473)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- ABCA1, cholesterol efflux, amyloid-beta, Alzheimer's disease, liver X receptor, apolipoprotein E, serum cholesterol, cholesterol homeostasis, cholesterol transporters
- MeSH terms
- Benzenesulfonamides, Animals, Biological Transport, Cholesterol, Dose-Response Relationship, Drug, Fluorocarbons, Cricetinae, Humans, Hydrocarbons, Fluorinated, Male, Mice, Inbred DBA, Sulfonamides, Up-Regulation, Amyloid beta-Peptides, CHO Cells, Mice, Knockout, ATP-Binding Cassette Transporters, Mice, ATP Binding Cassette Transporter 1
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