title: Striatal neuronal loss correlates with clinical motor impairment in Huntington's disease.
abstract: Huntington's disease (HD) is characterized clinically by chorea, motor impairment, psychiatric manifestations, and dementia. Atrophy of the striatum is the neuropathological hallmark of HD, and previous studies have suggested that striatal atrophy correlates more closely with motor impairment than with chorea. Motor impairment, as measured by motor impairment score, correlates with functional disability in HD patients, but chorea does not. In this study, we investigated the relation between neuronal loss and these motor features. We conducted neuropathological and stereologic assessments of neurons in putamen and subthalamic nuclei in HD patients and age-matched controls. In putamen, we estimated the total number and volume of medium spiny neurons labeled with dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP-32). In subthalamic nuclei, we estimated the total number of neurons on hematoxylin & eosin/luxol fast blue stains. In putamen of HD, immunohistochemistry showed DARPP-32 neuronal atrophy with extensive disruption of neurites and neuropil; stereologic studies found significant decreases in both the number and size of DARPP-32 neurons; we also detected a significant reduction of overall putamen volume in HD patients, compared to controls. In subthalamic nuclei, there was a mild, but significant, neuronal loss in the HD group. The loss of neurons in putamen and subthalamic nuclei as well as putaminal atrophy were significantly correlated with severity of motor impairment, but not with chorea. Our findings suggest that neuronal loss and atrophy in striatum and neuronal loss in subthalamic nuclei contribute specifically to the motor impairment of HD, but not to chorea.
authors.affiliation: Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Guo
authors.forename: Gay
authors.initials: G
authors.lastname: Rudow
authors.forename: Olga
authors.initials: O
authors.lastname: Pletnikova
authors.forename: Kari-Elise
authors.initials: KE
authors.lastname: Codispoti
authors.forename: Brent A
authors.initials: BA
authors.lastname: Orr
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Crain
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Duan
authors.forename: Russell L
authors.initials: RL
authors.lastname: Margolis
authors.forename: Adam
authors.initials: A
authors.lastname: Rosenblatt
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001344:Autopsy; D016022:Case-Control Studies; D016923:Cell Death; D048429:Cell Size; D003342:Corpus Striatum / Q000473:pathology*; D004185:Disability Evaluation; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D013223:Statistics as Topic
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human