Increased ATP-binding cassette transporter A1 expression in Alzheimer's disease hippocampal neurons
Abstract
ATP-binding cassette transporter A1 (ABCA1) reduces amyloid-beta burden in transgenic mouse models of Alzheimer's disease (AD). Associations between ABCA1 polymorphisms and AD risk are also established. Little is known regarding the regulation of ABCA1 expression in the brain and how this may be affected by AD. In the present study we assessed ABCA1 mRNA and protein expression in the hippocampus of AD cases compared to controls. ABCA1 was clearly expressed in hippocampal neurons and expression was increased two- to three-fold in AD cases. The increased hippocampal ABCA1 expression was associated with increased APOE and PUMA gene expression, implying an association with neuronal stress. Consistent with this, treatment of SK-N-SH neurons with amyloid-beta peptide resulted in a 48% loss in survival and a significant upregulation of ABCA1, APOE, and PUMA gene expression. Studies in young (2 month) and old (12 month) transgenic mice expressing a familial AD form of human amyloid-beta protein precursor and presenilin-1 revealed a significant age-dependent upregulation of hippocampal Abca1 compared to wild-type control mice. However, hippocampal Apoe and Puma gene expression were not correlated with increased Abca1 expression in mice. Our data indicate that ABCA1 is upregulated in AD hippocampal neurons potentially via an amyloid-beta-mediated pathway.
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Induction of ABCA1 in AD brains was mainly due to increased neuronal expression.
“Induction of ABCA1 in AD brains was mainly due to increased neuronal expression (Kim et al., 2010)”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Kim et al., 2010
ABCA1 expression was increased in the hippocampus of AD cases as well as an AD mouse model.
“Recent studies reported that ABCA1 expression was increased in the hippocampus of AD cases as well as an AD mouse model (Akram et al., 2010; Kim et al., 2010).”
From miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression (2012) · cites this paper as Kim et al., 2010
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- Authors
- Kim, W. S., Bhatia, S., Elliott, D. A., Agholme, L., Kågedal, K., McCann, H., Halliday, G. M., Barnham, K. J., & Garner, B.
- Affiliations
- UNSW Sydney (AU)
- Neuroscience Research Australia (AU)
- The University of Melbourne (AU)
- University of Wollongong (AU)
- Corresponding author
- Garner, Brett
- ORCID
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-07-08
- Volume
- 21
- Issue
- 1
- Pages
- 193-205
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1536336594
- Cited by
- 40
- References
- 0
- Citations by year
- 2023: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 8
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- ABCA1, Alzheimer's disease
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Apolipoproteins E, Cerebellum, Cricetulus, Female, Gene Expression Regulation, Cricetinae, Hippocampus, Humans, Male, Neuroblastoma, Neurons, Protein Binding, Proto-Oncogene Proteins, RNA, Messenger, Time Factors, Transfection, CHO Cells, ATP-Binding Cassette Transporters, Cell Line, Tumor, Apoptosis Regulatory Proteins, Mice, ATP Binding Cassette Transporter 1
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