Abstract
Transgenic Huntington’s disease monkey (HD monkey) model provides great opportunity for studying disease progression that could lead to new insight for developing biomarker, early intervention and novel therapeutics. Whole brain white matter integrity of HD-monkeys was examined longitudinally from 6 to 48 months using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). Progressive developmental white matter alterations in HD monkeys were widespread and were observed not only in fiber bundles connecting cortical areas to the striatum (e.g. striatal bundle and external capsule), but also in long association fiber pathways, commissural fibers, and subcortical fiber bundle. In all fiber tracts, the data indicate an arrest in white matter development around 23 months followed by slight decline until adulthood in HD monkeys. The microstructural changes parallel the progressive motor, memory and cognitive decline previously reported as HD monkeys aged. The findings revealed the widespread progressive temporal-spatial microstructural changes in HD monkey brains from infancy to adulthood, suggesting differentiated degenerations across different brain areas during brain development.
Highlights
Transgenic Huntington’s disease monkey (HD monkey) model provides great opportunity for studying disease progression that could lead to new insight for developing biomarker, early intervention and novel therapeutics
These regions of interest (ROIs) were selected for further analyses and included cortical areas, such as the right medial primary motor cortex, the left ventral intraparietal cortex (VIP), and the anterior temporal area (TAa) bilaterally
Further analyses indicated that the maximal Fractional anisotropy (FA) value was reached at a younger age for the HD monkeys (22.7 ± 4.8 months) than for the controls (47.8 ± 11.7), revealing an arrest of white matter maturation in the HD group predicted by Poisson model (Fig. 3a,c,e and g; see Table 1 for details)
Summary
Transgenic Huntington’s disease monkey (HD monkey) model provides great opportunity for studying disease progression that could lead to new insight for developing biomarker, early intervention and novel therapeutics. Whole brain white matter integrity of HD-monkeys was examined longitudinally from 6 to 48 months using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). The data indicate an arrest in white matter development around 23 months followed by slight decline until adulthood in HD monkeys. The microstructural changes parallel the progressive motor, memory and cognitive decline previously reported as HD monkeys aged. The development of an animal model with similar genetic constitution, progressive decline in measurable clinical features and neuroanatomical structures, is important for studying HD pathogenesis, the development of biomarkers and novel therapeutics[8, 9]. White matter fiber connections between striatum and prefrontal cortex or motor domains in primates are well established[16]. Changes of microglia cells, astrocytosis, neuronal remodeling, or loss of specific fiber tracts could change FA and diffusivities in brain structures[23, 24]
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