Lipoprotein Receptor-Related Protein-1 Mediates Amyloid-β-Mediated Cell Death of Cerebrovascular Cells
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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-med…
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LRP1 mediates cellular uptake of Aβ followed by its intracellular degradation and clearance.
“which mediates cellular uptake of A 𝛃 followed by its intracellular degradation and clearance (513, 647).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [647]
In the case of excessive Aβ load, accumulation of Aβ can lead to pericyte cell death.
“In the case of excessive A 𝛃 load, accumulation of A 𝛃 can lead to pericyte cell death (513, 647).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [647]
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“Cerebrovascular CD36 expression in AD brains is increased and is linked to CAA [29].”
Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection
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Apolipoprotein E and LRP1 Increase Early in Parkinson's Disease Pathogenesis
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Self-citationDocosahexaenoic Acid Reduces Amyloid-β Induced Toxicity in Cells of the Neurovascular Unit
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Pericyte Plasticity in the Brain
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The Imbalance of Vascular Molecules in Alzheimer's Disease
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Self-citation
- Authors
- Wilhelmus, M. M. M., Otte-Höller, I., van Triel, J. J. J., Veerhuis, R., Maat-Schieman, M. L. C., Bu, G., de Waal, R. M. W., & Verbeek, M. M.
- Affiliations
- Radboud University Medical Center (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Washington University in St. Louis (US)
- Corresponding author
- Verbeek, Marcel M.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 171
- Issue
- 6
- Pages
- 1989-1999
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2111121
- OpenAlex
- W2060117322
- Cited by
- 138
- References
- 50
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 7 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 12
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Hersenstichting (14F06.18)
- Internationale Stichting Alzheimer Onderzoek (03517)
- National Institutes of Health (AG027924)
- National Institute on Aging (R01AG027924, R37AG027924, AG027924)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- amyloid-beta, Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis-Dutch type, cerebral amyloid angiopathy, LDL receptor, CD36, receptor for advanced glycation end products, pericytes, receptor-associated protein, blood-brain barrier, astrocytes
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Blood Vessels, Blood-Brain Barrier, Brain, Female, Humans, Male, Receptors, LDL, Amyloid beta-Peptides, Apoptosis, CD36 Antigens, Pericytes, Low Density Lipoprotein Receptor-Related Protein-1, Cerebral Amyloid Angiopathy, Familial
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