Lipoprotein receptor-related protein-1 mediates amyloid- -mediated cell death of cerebrovascular cells
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Am J Pathol. 2007 Dec;171(6):1989-99. Epub 2007 Nov 30
Wilhelmus MM, Otte-Holler I, van Triel JJ, Veerhuis R, Maat-Schieman ML, Bu G, de Waal RM, Verbeek MM.
Department of Neurology, 830 LKN, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Inefficient clearance of Abeta, caused by impaired blood-brain barrier crossing into the circulation, seems to be a major cause of Abeta accumulation in the brain of late-onset Alzheimer's disease patients and hereditary cerebral hemorrhage with amyloidosis Dutch type. We observed association of receptor for advanced glycation end products, CD36, and low-density lipoprotein receptor (LDLR) with cerebral amyloid angiopathy in both Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis Dutch type brains and increased low-density lipoprotein receptor-related protein-1 (LRP-1) expression by perivascular cells in cerebral amyloid angiopathy. We investigated if these Abeta receptors are involved in Abeta internalization and in Abeta-mediated cell death of human cerebrovascular cells and astrocytes. Expression of both the LRP-1 and LDLR by human brain pericytes and leptomeningeal smooth muscle cells, but not by astrocytes, increased on incubation with Abeta. Receptor-associated protein specifically inhibited Abeta-mediated up-regulation of LRP-1, but not of LDLR, and receptor-associated protein also decreased Abeta internalization and Abeta-mediated cell death. We conclude that especially LRP-1 and, to a minor extent, LDLR are involved in Abeta internalization by and Abeta-mediated cell death of cerebral perivascular cells. Although perivascular cells may adapt their Abeta internalization capacity to the levels of Abeta present, saturated LRP-1/LDLR-mediated uptake of Abeta results in degeneration of perivascular cells.
PubMed ID and Record
Am J Pathol. 2007 Dec;171(6):1989-99. Epub 2007 Nov 30
Wilhelmus MM, Otte-Holler I, van Triel JJ, Veerhuis R, Maat-Schieman ML, Bu G, de Waal RM, Verbeek MM.
Department of Neurology, 830 LKN, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Inefficient clearance of Abeta, caused by impaired blood-brain barrier crossing into the circulation, seems to be a major cause of Abeta accumulation in the brain of late-onset Alzheimer's disease patients and hereditary cerebral hemorrhage with amyloidosis Dutch type. We observed association of receptor for advanced glycation end products, CD36, and low-density lipoprotein receptor (LDLR) with cerebral amyloid angiopathy in both Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis Dutch type brains and increased low-density lipoprotein receptor-related protein-1 (LRP-1) expression by perivascular cells in cerebral amyloid angiopathy. We investigated if these Abeta receptors are involved in Abeta internalization and in Abeta-mediated cell death of human cerebrovascular cells and astrocytes. Expression of both the LRP-1 and LDLR by human brain pericytes and leptomeningeal smooth muscle cells, but not by astrocytes, increased on incubation with Abeta. Receptor-associated protein specifically inhibited Abeta-mediated up-regulation of LRP-1, but not of LDLR, and receptor-associated protein also decreased Abeta internalization and Abeta-mediated cell death. We conclude that especially LRP-1 and, to a minor extent, LDLR are involved in Abeta internalization by and Abeta-mediated cell death of cerebral perivascular cells. Although perivascular cells may adapt their Abeta internalization capacity to the levels of Abeta present, saturated LRP-1/LDLR-mediated uptake of Abeta results in degeneration of perivascular cells.
PubMed ID and Record
posted by Dr.Koudinov @ 1:19 AM
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