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

作者：Fujiyoshi Masachika; Tachikawa Masanori; Ohtsuki Sumio; Ito Shingo; Uchida Yasuo; Akanuma Shin ichi; Kamiie Junichi; Hashimoto Tadafumi; Hosoya Ken ichi; Iwatsubo Takeshi; Terasaki Tetsuya^*

来源：Journal of Neurochemistry, 2011, 118(3): 407-415.

DOI：10.1111/j.1471-4159.2011.07311.x

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

Amyloid-beta peptide (A beta) 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 A beta(1-40) [hA beta (1-40)] from CSF. After intracerebroventricular (ICV) administration, [(125)I] hA beta(1-40) was eliminated from the rat CSF with a half-life of 17.3 min. The elimination of [(125)I] hA beta(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 hA beta(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/mu g protein, whereas the LRP2 content was below the detection limit (<0.2 fmol/mu g protein). Conditionally, immortalized rat choroid plexus epithelial cells exhibited predominant apical-to-basal and apical-to-cell transport of [(125)I] hA beta(1-40). These results indicated that hA beta(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 hA beta(1-40).

• 出版日期2011-8