Blood–brain barrier dysfunction in parkinsonian midbrain in vivo

TLDR

Parkinson’s disease involves loss of midbrain neurons, and while its cause remains unknown, neurotoxins can induce similar syndromes; the blood–brain barrier protects the brain via efflux pumps such as P‑glycoprotein, whose genetic vulnerability may influence disease risk. 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, a substrate normally extruded by P‑gp. PD patients showed a 18% increase in [11C]‑verapamil uptake in the midbrain, providing the first evidence that a dysfunctional blood–brain barrier contributes to Parkinson’s disease. Published in Annals of Neurology, 2005;57:176–179.

Abstract

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. Ann Neurol 2005;57:176–179