title: Progressive cognitive deficit, motor impairment and striatal pathology in a transgenic Huntington disease monkey model from infancy to adulthood.
abstract: One of the roadblocks to developing effective therapeutics for Huntington disease (HD) is the lack of animal models that develop progressive clinical traits comparable to those seen in patients. Here we report a longitudinal study that encompasses cognitive and motor assessment, and neuroimaging of a group of transgenic HD and control monkeys from infancy to adulthood. Along with progressive cognitive and motor impairment, neuroimaging revealed a progressive reduction in striatal volume. Magnetic resonance spectroscopy at 48 months of age revealed a decrease of N-acetylaspartate (NAA), further suggesting neuronal damage/loss in the striatum. Postmortem neuropathological analyses revealed significant neuronal loss in the striatum. Our results indicate that HD monkeys share similar disease patterns with HD patients, making them potentially suitable as a preclinical HD animal model.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Anthony W S
authors.initials: AW
authors.lastname: Chan
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Yiju
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Prucha
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, Georgia, United States of America.
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Tim
authors.initials: T
authors.lastname: Chi
authors.affiliation: Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Sean
authors.initials: S
authors.lastname: Moran
authors.affiliation: Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Tayeb
authors.initials: T
authors.lastname: Rahim
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Shihua
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Zola
authors.affiliation: Department of Neurology and Parkinson's and Movement Disorders Center, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Testa
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.affiliation: Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Rosa
authors.initials: R
authors.lastname: Villalba
authors.affiliation: Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America; Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Yoland
authors.initials: Y
authors.lastname: Smith
authors.affiliation: Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America; Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Psychology, Emory University School of Medicine, Atlanta, Georgia, United States of America; Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Center, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Bachevalier
mesh_terms: D000818:Animals; D003071:Cognition; D003342:Corpus Striatum / Q000254:growth & development / Q000473:pathology*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008253:Macaca mulatta; D008297:Male; D009048:Motor Skills; D019076:Transgenes