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

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)407-415
Number of pages9
JournalJournal of Neurochemistry
Volume118
Issue number3
DOIs
Publication statusPublished - Aug 1 2011
Externally publishedYes

Keywords

  • Alzheimer's disease
  • amyloid-β peptide
  • blood-cerebrospinal fluid barrier
  • choroid plexus
  • conditionally immortalized rat choroid plexus epithelial cell line cells
  • low-density lipoprotein receptor-related protein-1

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Amyloid-β peptide(1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier'. Together they form a unique fingerprint.

  • Cite this

    Fujiyoshi, M., Tachikawa, M., Ohtsuki, S., Ito, S., Uchida, Y., Akanuma, S. I., Kamiie, J., Hashimoto, T., Hosoya, K. I., Iwatsubo, T., & Terasaki, T. (2011). Amyloid-β peptide(1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier. Journal of Neurochemistry, 118(3), 407-415. https://doi.org/10.1111/j.1471-4159.2011.07311.x