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) 118 , 407–415. 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).