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

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• 作者：Shin-ichi Akanuma ; Sumio Ohtsuki ; Youko Doi ; Masanori Tachikawa ; Shingo Ito ; Satoko Hori ; Tomoko Asashima ; Tadafumi Hashimoto ; Kaoru Yamada ; Kazumitsu Ueda ; Takeshi Iwatsubo ; Tetsuya Terasaki
• 关键词：Alzheimer's disease ; ATP-binding cassette transporter ; Mouse blood– ; brain barrier ; Amyloid-β ; peptide (1– ; 40) ; ABCA1 ; Mouse brain efflux index study ; ABCA1 knockout mouse ; LXR
• 刊名：Neurochemistry International
• 出版年：2008
• 期刊代码：120_01970186
• 类别：bio
• 出版时间：May 2008
• 卷：52
• 期：6
• 页码：956-961
• 文件大小：223 K

摘要

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.