Blood-brain barrier dysfunction in parkinsonian midbrain in vivo.
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.
Kortekaas
Rudie
R
Department of Neurology, Groningen University Hospital, Groningen, The Netherlands.
Leenders
Klaus L
KL
van Oostrom
Joost C H
JC
Vaalburg
Willem
W
Bart
Joost
J
Willemsen
Antoon T M
AT
Hendrikse
N Harry
NH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000368:Aged; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D014700:Verapamil / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014700:Verapamil