Extrastriatal dopamine D 2 receptor binding in Huntington's disease

Abstract

Huntington's disease (HD) is a neurodegenerative disorder, primarily affecting medium spiny neurones in the striatum. The density of striatal dopamine D 2 receptors is reduced in HD but there is little known about this biomarker in brain regions outside the striatum. The primary objective of this study was to compare extrastriatal dopamine D 2 receptor binding, in age-matched control subjects and patients with HD. All subjects were examined using a high-resolution positron emission tomography system and the high-affinity dopamine D 2 receptor radioligand [ 11C]FLB 457. A ROI based analysis was used with an atrophy correction method. Dopamine D 2 receptor binding potential was reduced in the striatum of patients with HD. Unlike the striatum, dopamine D 2 receptor binding in thalamic and cortical subregions was not significantly different from that in control subjects. A partial least square regression analysis which included binding potential values from all investigated cortical and subcortical regions revealed a significant model separating patients from controls, conclusively dependent on differences in striatal binding of the radioligand. Some clinical assessments correlated with striatal dopamine D 2 receptor binding, including severity of chorea and cognitive test performance. Hence, the present study demonstrates that dopamine D 2 receptors extrinsic to the striatum are well preserved in early to mid stage patients with HD. This observation may have implication for the development of therapy for HD. © 2010 Wiley-Liss, Inc.