Amyloid-β peptide(1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier

Masachika Fujiyoshi, Masanori Tachikawa, Sumio Ohtsuki, Shingo Ito, Yasuo Uchida, Shin Ichi Akanuma, Junichi Kamiie, Tadafumi Hashimoto, Ken Ichi Hosoya, Takeshi Iwatsubo, Tetsuya Terasaki

研究成果査読

46 被引用数 (Scopus)

抄録

Amyloid-β peptide (Aβ) concentration in CSF is potentially a diagnostic and therapeutic target for Alzheimer's disease (AD). The purpose of this study was to clarify the elimination mechanism of human Aβ(1-40) [hAβ (1-40)] from CSF. After intracerebroventricular (ICV) administration, [125I]hAβ(1-40) was eliminated from the rat CSF with a half-life of 17.3 min. The elimination of [125I]hAβ(1-40) was significantly inhibited by human receptor-associated protein (RAP) and the elimination was attenuated in either anti-low-density lipoprotein receptor-related protein (LRP)1 antibody-treated or RAP-deficient mice, suggesting that a member(s) of the low-density lipoprotein receptor gene family is involved in the elimination of hAβ(1-40) from CSF. The amounts of LRP1 and LRP2 proteins were determined by means of liquid chromatography-tandem mass spectrometry, and the LRP1 content in rat choroid plexus was determined to be 3.7 fmol/μg protein, whereas the LRP2 content was below the detection limit (< 0.2 fmol/μg protein). Conditionally, immortalized rat choroid plexus epithelial cells exhibited predominant apical-to-basal and apical-to-cell transport of [125I]hAβ(1-40). These results indicated that hAβ(1-40) is actively eliminated from CSF and this process is at least partly mediated by LRP1 expressed at choroid plexus epithelial cells, which therefore play a role in determining CSF concentrations of hAβ(1-40).

本文言語English
ページ(範囲)407-415
ページ数9
ジャーナルJournal of Neurochemistry
118
3
DOI
出版ステータスPublished - 8月 2011
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 細胞および分子神経科学

フィンガープリント

「Amyloid-β peptide(1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル