| First Author | Devraj K | Year | 2016 |
| Journal | J Cereb Blood Flow Metab | Volume | 36 |
| Issue | 7 | Pages | 1281-94 |
| PubMed ID | 26661166 | Mgi Jnum | J:318355 |
| Mgi Id | MGI:6859328 | Doi | 10.1177/0271678X15606463 |
| Citation | Devraj K, et al. (2016) BACE-1 is expressed in the blood-brain barrier endothelium and is upregulated in a murine model of Alzheimer's disease. J Cereb Blood Flow Metab 36(7):1281-94 |
| abstractText | Endothelial cells of the blood-brain barrier form a structural and functional barrier maintaining brain homeostasis via paracellular tight junctions and specific transporters such as P-glycoprotein. The blood-brain barrier is responsible for negligible bioavailability of many neuroprotective drugs. In Alzheimer's disease, current treatment approaches include inhibitors of BACE-1 (beta-site of amyloid precursor protein cleaving enzyme), a proteinase generating neurotoxic beta-amyloid. It is known that BACE-1 is highly expressed in endosomes and membranes of neurons and glia. We now provide evidence that BACE-1 is expressed in blood-brain barrier endothelial cells of human, mouse, and bovine origin. We further show its predominant membrane localization by 3D-dSTORM super-resolution microscopy, and by biochemical fractionation that further shows an abluminal distribution of BACE-1 in brain microvessels. We confirm its functionality in processing APP in primary mouse brain endothelial cells. In an Alzheimer's disease mouse model we show that BACE-1 is upregulated at the blood-brain barrier compared to healthy controls. We therefore suggest a critical role for BACE-1 at the blood-brain barrier in beta-amyloid generation and in vascular aspects of Alzheimer's disease, particularly in the development of cerebral amyloid angiopathy. |
