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

36 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

Fingerprint

ATP-Binding Cassette Transporters
Blood-Brain Barrier
Amyloid
Peptides
Brain
HEK293 Cells
Cholesterol
Apolipoproteins
Apolipoprotein A-I
Amyloid Plaques
Cerebrum
Knockout Mice
Membranes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

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. / 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.

In: Neurochemistry International, Vol. 52, No. 6, 01.05.2008, p. 956-961.

Research output: Contribution to journalArticle

Akanuma, SI, 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, vol. 52, no. 6, pp. 956-961. https://doi.org/10.1016/j.neuint.2007.12.002
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. / 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. In: Neurochemistry International. 2008 ; Vol. 52, No. 6. pp. 956-961.
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