title: ATP-binding cassette transporter A1 (ABCA1) deficiency does not attenuate the brain-to-blood efflux transport of human amyloid-beta 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.
authors.affiliation: Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Akanuma
authors.forename: Sumio
authors.initials: S
authors.lastname: Ohtsuki
authors.forename: Youko
authors.initials: Y
authors.lastname: Doi
authors.forename: Masanori
authors.initials: M
authors.lastname: Tachikawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Ito
authors.forename: Satoko
authors.initials: S
authors.lastname: Hori
authors.forename: Tomoko
authors.initials: T
authors.lastname: Asashima
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamada
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Terasaki
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001693:Biological Transport, Active / Q000235:genetics; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002460:Cell Line; D002536:Cerebral Arteries / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008845:Microinjections; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D016632:Apolipoprotein A-I; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)