Decreased blood-brain barrier P-glycoprotein function in the progression of Parkinson's disease, PSP and MSA.
Decreased blood-brain barrier (BBB) efflux function of the P-glycoprotein (P-gp) transport system could facilitate the accumulation of toxic compounds in the brain, increasing the risk of neurodegenerative pathology such as Parkinson's disease (PD). This study investigated in vivo BBB P-gp function in patients with parkinsonian neurodegenerative syndromes, using [11C]-verapamil PET in PD, PSP and MSA patients. Regional differences in distribution volume were studied using SPM with higher uptake interpreted as reduced P-gp function. Advanced PD patients and PSP patients had increased [11C]-verapamil uptake in frontal white matter regions compared to controls; while de novo PD patients showed lower uptake in midbrain and frontal regions. PSP and MSA patients had increased uptake in the basal ganglia. Decreased BBB P-gp function seems a late event in neurodegenerative disorders, and could enhance continuous neurodegeneration. Lower [11C]-verapamil uptake in midbrain and frontal regions of de novo PD patients could indicate a regional up-regulation of P-gp function.
Bartels
A L
AL
Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. a.l.bartels@neuro.umcg.nl
Willemsen
A T M
AT
Kortekaas
R
R
de Jong
B M
BM
de Vries
R
R
de Klerk
O
O
van Oostrom
J C H
JC
Portman
A
A
Leenders
K L
KL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000000981:diagnostic imaging / Q000473:pathology*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging / Q000473:pathology*; D014700:Verapamil / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002247:Carbon Isotopes; D014700:Verapamil