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

J Neurochem. 2011 Aug;118(3):407-15. doi: 10.1111/j.1471-4159.2011.07311.x. Epub 2011 Jun 17.


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, [(125) I]hAβ(1-40) was eliminated from the rat CSF with a half-life of 17.3 min. The elimination of [(125) I]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 [(125) I]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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Animals
  • Biological Transport, Active / physiology
  • Blood-Brain Barrier / physiology*
  • Cell Line
  • Choroid Plexus / cytology
  • Injections, Intraventricular
  • Kinetics
  • Low Density Lipoprotein Receptor-Related Protein-1 / blood
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Low Density Lipoprotein Receptor-Related Protein-2 / blood
  • Low Density Lipoprotein Receptor-Related Protein-2 / metabolism
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / cerebrospinal fluid*
  • Rats
  • Rats, Sprague-Dawley


  • Amyloid beta-Peptides
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Peptide Fragments
  • amyloid beta-protein (1-40)