Blood–brain barrier dysfunction in parkinsonian midbrain in vivo
Abstract
Parkinson's disease (PD) is associated with a loss of neurons from the midbrain. The cause of PD is unknown, but it is established that certain neurotoxins can cause similar syndromes. The brain is normally protected from these noxious blood-borne chemicals by the blood-brain barrier which includes specialized proteins on the inside of blood vessels in the brain. These act as molecular efflux pumps and P-glycoprotein (P-gp) is an abundant representative. Vulnerability to PD appears codetermined by the genotype for the P-gp gene. We hypothesized that PD patients have reduced P-gp function in the blood-brain barrier. We used positron emission tomography to measure brain uptake of [(11)C]-verapamil, which is normally extruded from the brain by P-gp. Here, we show significantly elevated uptake of [(11)C]-verapamil (18%) in the midbrain of PD patients relative to controls. This is the first evidence supporting a dysfunctional blood-brain barrier as a causative mechanism in PD.
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ABCB1 (P-gp) has reduced expression in vivo in PD patients.
“Highly expressed at the BBB endothelium, MDR1 encodes for ABCB1 (P-gp) that has reduced expression in vivo in PD patients, and is proposed to contribute to PD progression (327).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [327]
MDR1 is highly expressed at the BBB endothelium and encodes ABCB1 (P-gp).
“Highly expressed at the BBB endothelium, MDR1 encodes for ABCB1 (P-gp) that has reduced expression in vivo in PD patients, and is proposed to contribute to PD progression (327).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [327]
In Parkinson's disease patients, diminished activity of ABCB1 (P-gp) in mid-brain regions has been shown by [11C]verapamil PET.
“Diminished activity of a major BBB active efflux transporter ABCB1 (P-gp) has been shown in the mid-brain regains of PD patients by accumulation of [ 11 C]verapamil using PET technique (327).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [327]
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- Authors
- Kortekaas, R., Leenders, K. L., van Oostrom, J. C. H., Vaalburg, W., Bart, J., Willemsen, A. T. M., & Hendrikse, N. H.
- Affiliations
- University Medical Center Groningen (NL)
- Corresponding author
- Leenders, Klaus L.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2005-01-24
- Volume
- 57
- Issue
- 2
- Pages
- 176-179
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2001408101
- Cited by
- 733
- References
- 1
- Citations by year
- 2026: 14 · 2025: 34 · 2024: 41 · 2023: 35 · 2022: 53 · 2021: 49 · 2020: 53 · 2019: 33 · 2018: 42 · 2017: 30 · 2016: 30 · 2015: 32 · 2014: 41 · 2013: 33 · 2012: 30
- FWCI
- 19.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Parkinson's disease, blood-brain barrier dysfunction, P-glycoprotein, midbrain, efflux pumps, positron emission tomography
- MeSH terms
- Aged, Blood-Brain Barrier, Female, Humans, Male, Mesencephalon, Middle Aged, Parkinson Disease, Verapamil, ATP Binding Cassette Transporter, Subfamily B, Member 1, Positron-Emission Tomography
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