Changes in striatal dopamine D2 receptor binding in pre-clinical Huntington's disease.
BACKGROUND
Carriers of the Huntington disease (HD) mutation develop a progressive neurodegenerative disorder after a pre-clinical phase. We examined the value of (11)C-raclopride PET (RAC) as a biomarker for pre-clinical HD pathophysiology.


METHODS
In a prospective cohort study with clinical and neuropsychological assessment we collected complete RAC data in 18 pre-clinical mutation carriers (HD-PMC) and 11 controls. Follow-up was 2 years. We calculated striatal RAC binding potential (BP) to measure dopamine D2 receptor availability.


RESULTS
No HD-PMC had overt neuropsychological dysfunction. RAC-BP in putamen was abnormal in up to 44% of HD-PMC. The rate of RAC-BP decline (2.6% per year) was not significantly higher than in controls. Follow-up putaminal BP correlated weakly with predicted distance to onset of clinical HD (P = 0.034), but the rate of decline did not. Three HD-PMC developed motor abnormalities suspect for HD but did not show an increased rate of decline of putaminal BP.


CONCLUSIONS
Many HD-PMC have striatal abnormalities but we found no clearly increased rate of D2 receptor changes around the onset of clinical HD. A longer follow-up of the present study cohort is needed to establish the value of RAC-BP in assessing the risk of clinical conversion from striatal D2 binding data.
van Oostrom
J C H
JC
Department of Neurology, University Medical Center Groningen, The University of Groningen, Groningen, The Netherlands. j.c.h.van.oostrom@neuro.umcg.nl
Dekker
M
M
Willemsen
A T M
AT
de Jong
B M
BM
Roos
R A C
RA
Leenders
K L
KL
D000328:Adult; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006579:Heterozygote; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009483:Neuropsychological Tests; D009687:Nuclear Proteins / Q000235:genetics; D049268:Positron-Emission Tomography; D020891:Raclopride; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D020891:Raclopride