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

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, [(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).

journal_name

J Neurochem

authors

Fujiyoshi M,Tachikawa M,Ohtsuki S,Ito S,Uchida Y,Akanuma S,Kamiie J,Hashimoto T,Hosoya K,Iwatsubo T,Terasaki T

doi

10.1111/j.1471-4159.2011.07311.x

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

407-15

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

118

pub_type

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