| First Author | Rauch SM | Year | 2011 |
| Journal | J Neuropathol Exp Neurol | Volume | 70 |
| Issue | 12 | Pages | 1124-37 |
| PubMed ID | 22082664 | Mgi Jnum | J:220073 |
| Mgi Id | MGI:5632127 | Doi | 10.1097/NEN.0b013e31823b0b12 |
| Citation | Rauch SM, et al. (2011) Changes in brain beta-amyloid deposition and aquaporin 4 levels in response to altered agrin expression in mice. J Neuropathol Exp Neurol 70(12):1124-37 |
| abstractText | Conditions that compromise the blood-brain barrier (BBB) have been increasingly implicated in the pathogenesis of Alzheimer disease (AD). AGRIN is a heparan sulfate proteoglycan found abundantly in basement membranes of the cerebral vasculature, where it has been proposed to serve a functional role in the BBB. Furthermore, AGRIN is the major heparan sulfate proteoglycan associated with amyloid plaques in AD brains. To examine the relationship of AGRIN, the BBB, and AD-related pathologies, we generated mice in which the Agrn gene was deleted from either endothelial cells or neurons using gene targeting or was overexpressed using a genomic transgene construct. These mice were combined with a transgenic model of AD that over expresses disease-associated forms of amyloid precursor protein and presenilin 1. In mice lacking endothelial cell expression of Agrn, the BBB remained intact but aquaporin 4 levels were reduced, indicating that the loss of AGRIN affects BBB-associated components. This change in Agrn resulted in an increase in beta-amyloid (Abeta) in the brain. Conversely, overexpression of Agrn decreased Abeta deposition, whereas elimination of Agrn from neurons did not change Abeta levels. These results indicate that AGRIN is important for maintaining BBB composition and that changes in Agrn expression (particularly vessel-associated AGRIN) influence Abeta homeostasis in mouse models of AD. |
