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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)956-961
Number of pages6
JournalNeurochemistry International
Volume52
Issue number6
DOIs
Publication statusPublished - 2008 May 1
Externally publishedYes

Keywords

  • ABCA1
  • ABCA1 knockout mouse
  • ATP-binding cassette transporter
  • Alzheimer's disease
  • Amyloid-β peptide (1-40)
  • LXR
  • Mouse blood-brain barrier
  • Mouse brain efflux index study

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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  • Cite this

    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. (2008). 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. Neurochemistry International, 52(6), 956-961. https://doi.org/10.1016/j.neuint.2007.12.002