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Open Access Highly Accessed Research article

A two years longitudinal study of a transgenic Huntington disease monkey

Anthony WS Chan12*, Yan Xu12, Jie Jiang12, Tayeb Rahim1, Dongming Zhao12, Jannet Kocerha12, Tim Chi1, Sean Moran1, Heidi Engelhardt1, Katherine Larkin1, Adam Neumann1, Haiying Cheng12, Chunxia Li3, Katie Nelson1, Heather Banta1, Stuart M Zola14, Francois Villinger56, Jinjing Yang12, Claudia M Testa7, Hui Mao8, Xiaodong Zhang13 and Jocelyne Bachevalier109*

Author Affiliations

1 Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia

2 Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia

3 Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia

4 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia

5 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia

6 Division of Pathology, Yerkes National Primate Center, Emory University, Atlanta, Georgia

7 Department of Neurology, Emory University School of Medicine, Atlanta, Georgia

8 Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia

9 Department of Psychology, Emory University School of Medicine, Atlanta, Georgia

10 Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Center, Emory University, Atlanta, Georgia

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BMC Neuroscience 2014, 15:36  doi:10.1186/1471-2202-15-36

Published: 3 March 2014

Abstract

Background

A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington’s disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements.

Results

Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey.

Conclusions

This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment.