Original Article -annals of neurology

Blood-brain barrier dysfunction in parkinsonian midbrain in vivo

Rudie Kortekaas, PhD 1 2, Klaus L. Leenders, PhD 1 3 *, Joost C. H. van Oostrom, MD 1 3, Willem Vaalburg, PhD 5, Joost Bart, PhD 4, Antoon T. M. Willemsen, PhD 5, N. Harry Hendrikse, PhD 5
1Department of Neurology, Groningen University Hospital, Groningen, The Netherlands
2Anatomy and Embryology, Groningen University Hospital, Groningen, The Netherlands
3Movement Disorders Unit, Groningen University Hospital, Groningen, The Netherlands
4Department of Pathology, Groningen University Hospital, Groningen, The Netherlands
5PET-centre, Groningen University Hospital, Groningen, The Netherlands

email: Klaus L. Leenders (k.l.leenders@neuro.azg.nl)

*Correspondence to Klaus L. Leenders, Groningen University Hospital, Hanzeplein 1, 9700 RB, Groningen, The Netherlands

Funded by:
School for Behavioral and Cognitive Neurosciences

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 [11C]-verapamil, which is normally extruded from the brain by P-gp. Here, we show significantly elevated uptake of [11C]-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.

Ann Neurol 2005;57:176-179



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