Cited by 139Alzheimer's disease research and treatmentsBarrier Structure and Function StudiesIntracerebral and Subarachnoid Hemorrhage Research

Lipoprotein Receptor-Related Protein-1 Mediates Amyloid-β-Mediated Cell Death of Cerebrovascular Cells

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Wilhelmus, Micha M.M., Otte-Höller, Irene, van Triel, Jos J.J., Veerhuis, Robert, Maat-Schieman, Marion L.C., Bu, Guojun, de Waal, Robert M.W., Verbeek, Marcel M.·2007·The American Journal of Pathology

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-med…

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Registry

Crossref · 10.2353/ajpath.2007.070050

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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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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)
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
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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