Abstract
Inefficient clearance of A beta, caused by impaired blood-brain barrier crossing into the circulation, seems to be a major cause of A beta 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 A beta receptors are involved in A beta internalization and in A beta-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 A beta. Receptor-associated protein specifically inhibited A beta-mediated up-regulation of LRP-1, but not of LDLR, and receptor-associated protein also decreased A beta internalization and A beta-mediated cell death. We conclude that especially LRP-1 and, to a minor extent, LDLR are involved in A beta internalization by and A beta-mediated cell death of cerebral perivascular cells. Although perivascular cells may adapt their A beta internalization capacity to the levels of A beta present, saturated LRP-1/LDLR-mediated uptake of A beta results in degeneration of perivascular cells.
Original language | English |
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Pages (from-to) | 1989-99 |
Number of pages | 11 |
Journal | The American Journal of Pathology |
Volume | 171 |
Issue number | 6 |
DOIs | |
Publication status | Published - Dec 2007 |
Keywords
- Aged
- Aged, 80 and over
- Alzheimer Disease
- Amyloid beta-Peptides
- Apoptosis
- Blood Vessels
- Blood-Brain Barrier
- Brain
- CD36 Antigens
- Cerebral Amyloid Angiopathy, Familial
- Female
- Humans
- Journal Article
- Low Density Lipoprotein Receptor-Related Protein-1
- Male
- Pericytes
- Receptors, LDL
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't