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Cerebral clearance of human amyloid-β peptide (1–40) across the blood–brain barrier is reduced by self-aggregation and formation of low-density lipoprotein receptor-related protein-1 ligand complexes
| Content Provider | Scilit |
|---|---|
| Author | Ito, Shingo Ohtsuki, Sumio Kamiie, Junichi Nezu, Yasuko Terasaki, Tetsuya |
| Copyright Year | 2007 |
| Description | Journal: Journal of Neurochemistry Soluble amyloid-beta peptide (Abeta) exists in the form of monomers and oligomers, and as complexes with Abeta-binding molecules, such as low-density lipoprotein receptor-related protein-1 (LRP-1) ligands. The present study investigated the effect of self-aggregation and LRP-1 ligands on the elimination of human Abeta(1-40) [hAbeta(1-40)] from the rat brain across the blood-brain barrier. Incubation of [(125)I]hAbeta(1-40) monomer resulted in time-dependent and temperature-dependent dimer formation, and the apparent elimination rate of [(125)I]hAbeta(1-40) dimer was significantly decreased by 92.7% compared with that of [(125)I]hAbeta(1-40) monomer. Pre-incubation with LRP-1 ligands, such as activated alpha2-macroglobulin (alpha2M), apolipoprotein E2 (apoE2), apoE3, apoE4, and lactoferrin, reduced the elimination of [(125)I]hAbeta(1-40). By contrast, pre-administration of the same concentration of these molecules in the rat brain did not significantly inhibit [(125)I]hAbeta(1-40) monomer elimination. Purified [(125)I]hAbeta(1-40)/activated alpha2M complex and [(125)I]activated alpha2M were not significantly eliminated from the rat brain up to 60 min. MEF-1 cells, which have LRP-1-mediated endocytosis, exhibited uptake of [(125)I]activated alpha2M, and enhancement of [(125)I]hAbeta(1-40) uptake upon pre-incubation with apoE, suggesting that [(125)I]activated alpha2M and [(125)I]hAbeta(1-40)/apoE complex function as LRP-1 ligands. These findings indicate that dimerization and LRP-1-ligand complex formation prevent the elimination of hAbeta(1-40) from the brain across the blood-brain barrier. |
| Related Links | http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2007.04938.x/pdf |
| Ending Page | 2490 |
| Page Count | 9 |
| Starting Page | 2482 |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.2007.04938.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 6 |
| Volume Number | 103 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2007-12-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Biochemistry and Molecular Biology Alzheimer's Disease Amyloid‐β Peptide Blood–brain Barrier Low‐density Lipoprotein Receptor‐related Protein‐1 |
| Content Type | Text |
| Resource Type | Article |