ATP-binding cassette transporters P-glycoprotein and breast cancer related protein are reduced in capillary cerebral amyloid angiopathy
Abstract
Alzheimer's disease (AD) is the most common form of dementia and marked by deposition of amyloid-β (Aβ) within the brain. Alterations of Aβ transporters at the neurovasculature may play a role in the disease process. We investigated the expression of ABC transporters P-glycoprotein (P-gp) and breast cancer related protein (BCRP) in non-neurologic controls, AD, and severe capillary cerebral amyloid angiopathy (capCAA) cases, which are characterized by deposition of Aβ within cerebral capillaries. Our data show that microvascular expression of P-gp and BCRP is strikingly decreased in capCAA-affected vessels but not in AD and control samples. Messenger RNA levels of P-gp, but not of BCRP, were downregulated in brain endothelial cells on exposure to oligomeric Aβ42, but not fibrillar Aβ42 or Aβ40. Coincubating Aβ42 together with clusterin, an amyloid-associated protein highly expressed in capCAA-affected vessels, strongly reduced levels of P-gp. In conclusion, accumulation of Aβ, in combination with clusterin, within and around cerebral capillaries, may further aggravate the disease process in AD by affecting P-gp expression. Loss of P-gp expression or activity may serve as a selective biomarker for ongoing capCAA.
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In mouse model of AD and AD patients, BBB benefits clearance of Aβ aggregates through efflux of amyloid from brain by dedicated transporters such as LRP1 and P-glycoprotein.
“In mouse model of AD and AD patients, BBB benefits the clearance of Aβ aggregates through the efflux of amyloid from the brain by dedicated transporters, such as LRP1 (lipoprotein receptor-related protein-1) and P-glycoprotein,136,137”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [137]
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Role of neuroinflammation in neurodegeneration development
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Aging alters mRNA expression of amyloid transporter genes at the blood-brain barrier
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- Authors
- Carrano, A., Snkhchyan, H., Kooij, G., van der Pol, S., van Horssen, J., Veerhuis, R., Hoozemans, J., Rozemuller, A., & de Vries, H. E.
- Affiliations
- Amsterdam Neuroscience (NL)
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 35
- Issue
- 3
- Pages
- 565-575
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1963640795
- Cited by
- 51
- References
- 10
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 8 · 2019: 3 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 1 · 2014: 3
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- “Internationale Stichting Alzheimer Onderzoek” (07517, 09506)
- Erasmus Mundus Neuroscience Network
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- P-glycoprotein, ABC transporters, Alzheimer's disease, amyloid-beta, Aβ42 oligomers, clusterin, brain endothelial cells, cerebral microvasculature, amyloid-beta transport, biomarkers
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily G, Member 2, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Capillaries, Cells, Cultured, Female, Humans, Male, Neoplasm Proteins, Peptide Fragments, RNA, Messenger, Biomarkers, Down-Regulation, Gene Expression, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 1, Endothelial Cells, Clusterin
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