ATP-binding cassette transporter A1 (ABCA1) deficiency does not attenuate the brain-to-blood efflux transport of human amyloid-β peptide (1–40) at the blood–brain barrier
Abstract
ATP-binding cassette transporter A1 (ABCA1) mediates apolipoprotein-dependent cholesterol release from cellular membranes. Recent studies using ABCA1 knockout mice have demonstrated that ABCA1 affects amyloid-beta peptide (A beta) levels in the brain and the production of senile plaque. Cerebral A beta(1-40) was eliminated from the brain to the circulating blood via the blood-brain barrier (BBB), which expresses ABCA1. Therefore, in the present study, we examined whether ABCA1 affects the brain-to-blood efflux transport of human A beta(1-40)(hA beta(1-40)) at the BBB. The apparent uptake of [125I]hA beta(1-40) into ABCA1-expressing HEK293 cells was not significantly different from that into parental HEK293 cells. In addition, the apparent uptake was not significantly affected even in the presence of apolipoprotein A-I as a cholesterol release acceptor. Moreover, [125I]hA beta(1-40) elimination from mouse brain across the BBB was not significantly different between ABCA1-deficient and wild-type mice 60 min after its administration into the cerebrum. These results suggest that ABCA1 does not directly transport hA beta(1-40) and a deficiency of ABCA1 does not attenuate the brain-to-blood efflux transport of hA beta(1-40) across the BBB.
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A previous study measuring the disappearance of radiolabeled Aβ injected into the brains of ABCA1−/− mice found no effect on Aβ clearance across the blood-brain barrier.
“A previous study measuring the disappearance of radiolabeled Aβ injected into the brains of ABCA1−/− mice also found no effect on Aβ clearance across the blood–brain barrier [47].”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [47]
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- Authors
- Akanuma, S.-I., Ohtsuki, S., Doi, Y., Tachikawa, M., Ito, S., Hori, S., Asashima, T., Hashimoto, T., Yamada, K., Ueda, K., Iwatsubo, T., & Terasaki, T.
- Affiliations
- Tohoku University (JP)
- The University of Tokyo (JP)
- Kyoto University (JP)
- Corresponding author
- Terasaki, Tetsuya
- ORCID
- Venue
- Neurochemistry International
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 52
- Issue
- 6
- Pages
- 956-961
- ISSN
- 0197-0186 (ISSN-L)
- OpenAlex
- W2068330673
- Cited by
- 50
- References
- 2
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 7
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemistry International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- ABCA1, ABC transporters, amyloid-beta, Aβ(1-40), blood-brain barrier, efflux transport, apolipoprotein A-I, cholesterol efflux, amyloid-beta clearance, amyloid plaques
- MeSH terms
- Animals, Biological Transport, Active, Blood-Brain Barrier, Brain, Cell Line, Cerebral Arteries, Humans, Microinjections, Peptide Fragments, Amyloid beta-Peptides, Apolipoprotein A-I, Mice, Knockout, ATP-Binding Cassette Transporters, Endothelial Cells, Mice, ATP Binding Cassette Transporter 1
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