PLoS ONE (Jan 2015)

Progressive cognitive deficit, motor impairment and striatal pathology in a transgenic Huntington disease monkey model from infancy to adulthood.

  • Anthony W S Chan,
  • Jie Jiang,
  • Yiju Chen,
  • Chunxia Li,
  • Melinda S Prucha,
  • Yijuan Hu,
  • Tim Chi,
  • Sean Moran,
  • Tayeb Rahim,
  • Shihua Li,
  • Xiaojiang Li,
  • Stuart M Zola,
  • Claudia M Testa,
  • Hui Mao,
  • Rosa Villalba,
  • Yoland Smith,
  • Xiaodong Zhang,
  • Jocelyne Bachevalier

DOI
https://doi.org/10.1371/journal.pone.0122335
Journal volume & issue
Vol. 10, no. 5
p. e0122335

Abstract

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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.