| First Author | Pflanzner T | Year | 2011 |
| Journal | Neurobiol Aging | Volume | 32 |
| Issue | 12 | Pages | 2323.e1-11 |
| PubMed ID | 20630619 | Mgi Jnum | J:188234 |
| Mgi Id | MGI:5439721 | Doi | 10.1016/j.neurobiolaging.2010.05.025 |
| Citation | Pflanzner T, et al. (2011) LRP1 mediates bidirectional transcytosis of amyloid-beta across the blood-brain barrier. Neurobiol Aging 32(12):2323.e1-11 |
| abstractText | According to the "amyloid hypothesis", the amyloid-beta (Abeta) peptide is the toxic intermediate driving Alzheimer's disease (AD) pathogenesis. Recent evidence suggests that the low density lipoprotein receptor-related protein 1 (LRP1) transcytoses Abeta out of the brain across the blood-brain barrier (BBB). To provide genetic evidence for LRP1-mediated transcytosis of Abeta across the BBB we analyzed Abeta transcytosis across primary mouse brain capillary endothelial cells (pMBCECs) derived from wild-type and LRP1 knock-in mice. Here, we show that pMBCECs in vitro express functionally active LRP1. Moreover, we demonstrate that LRP1 mediates transcytosis of [(125)I]-Abeta(1-40) across pMBCECs in both directions, whereas no role for LRP1-mediated Abeta degradation was detected. Analysis of [(125)I]-Abeta(1-40) transport across pMBCECs generated from mice harboring a knock-in mutation in the NPxYxxL endocytosis/sorting domain of endogenous LRP1 revealed a reduced Abeta clearance from brain-to-blood and blood-to-brain compared with wild-type derived pMBCECs. Therefore, for the first time, we present genetic evidence that LRP1 modulates the pathogenic actions of soluble Abeta in the brain by clearing Abeta across the BBB. |
