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

• Published in: Neurochemistry international 2008-05, Vol.52 (6), p.956-961
• Main Authors: Akanuma, Shin-ichi, Ohtsuki, Sumio, Doi, Youko, Tachikawa, Masanori, Ito, Shingo, Hori, Satoko, Asashima, Tomoko, Hashimoto, Tadafumi, Yamada, Kaoru, Ueda, Kazumitsu, Iwatsubo, Takeshi, Terasaki, Tetsuya
• Format: Article
• Language: English
• Subjects: ABCA1; ABCA1 knockout mouse; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - pharmacology; Amyloid-β peptide (1–40); Animals; Apolipoprotein A-I - metabolism; ATP Binding Cassette Transporter 1; ATP-binding cassette transporter; ATP-Binding Cassette Transporters - genetics; Biological Transport, Active - genetics; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Brain - blood supply; Brain - metabolism; Cell Line; Cerebral Arteries - metabolism; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Humans; LXR; Mice; Mice, Knockout; Microinjections; Mouse blood–brain barrier; Mouse brain efflux index study; Peptide Fragments - metabolism; Peptide Fragments - pharmacology
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2007.12.002

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-β peptide (Aβ) levels in the brain and the production of senile plaque. Cerebral Aβ(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 Aβ(1–40)(hAβ(1–40)) at the BBB. The apparent uptake of [ 125I]hAβ(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]hAβ(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 hAβ(1–40) and a deficiency of ABCA1 does not attenuate the brain-to-blood efflux transport of hAβ(1–40) across the BBB.