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Assessment of cortical and striatal involvement in 523 Huntington disease brains
Abstract
Objective To evaluate the relationship of striatal involvement in Huntington disease (HD) to involvement in other brain regions, CAG repeat size, onset age, and other factors. Methods We examined patterns of neuropathologic involvement in 664 HD brains submitted to the Harvard Brain Tissue Resource Center. Brains with concomitant Alzheimer or Parkinson changes (n = 82), more than 20% missing data (n = 46), incomplete sample submission (n = 12), or CAG repeat less than 36 (n = 1) were excluded, leaving 523 cases. Standardized ratings from 0 (absent) to 4 (severe) of gross and microscopic involvement were performed for 50 regions. Cluster analysis reduced the data to 2 main measures of involvement: striatal and cortical. Results The clusters were correlated with each other (r = 0.42) and with disease duration (striatal: r = 0.35; cortical: r = 0.31). The striatal cluster was correlated with HD repeat size (r = 0.50). The cortical cluster showed a stronger correlation with decreased brain weight (r = -0.52) than the striatal cluster (r = -0.33). The striatal cluster was correlated with younger death age (r = -0.31) and onset age (r = -0.46) while the cortical cluster was not (r = 0.09, r = -0.04, respectively). Conclusions The 2 brain clusters had different relationships to the HD CAG repeat size, onset age, and brain weight, suggesting that neuropathologic involvement does not proceed in a strictly coupled fashion. The pattern and extent of involvement varies substantially from…
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“but experiences less extreme changes than the striatum [28,29]”
From miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement (2015) · cites this paper as [28]
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“To avoid confounding the analysis of these clinical features by the known, strong relationship between HTT CAG repeat size and disease pathology and onset [4,28,31,32], CAG-adjusted residuals were calculated for all continuous clinical traits”
From miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement (2015) · cites this paper as [28]
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“H-V scores are a continuous metric and therefore more amenable to adjustment of covariates such as CAG repeat size in modeling of neuropathological involvement and independently assesses striatal and cortical involvement.”
From miR-10b-5p expression in Huntington’s disease brain relates to age of onset and the extent of striatal involvement (2015) · cites this paper as [28]
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Hoss, A. G., Labadorf, A., Latourelle, J. C., Kartha, V. K., Hadzi, T. C., Gusella, J. F., MacDonald, M. E., Chen, J.-F., Akbarian, S., Weng, Z., et al. (2015) · BMC Medical Genomics · doi:10.1186/s12920-015-0083-3 · Cited by 151
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Metadata
- Authors
- Hadzi, T. C., Hendricks, A. E., Latourelle, J. C., Lunetta, K. L., Cupples, L. A., Gillis, T., Mysore, J. S., Gusella, J. F., MacDonald, M. E., Myers, R. H., & Vonsattel, J.-P.
- Affiliations
- From the Department of Neurology (T.C.H., J.C.L., R.H.M.), Boston University School of Medicine, Boston; Department of Biostatistics (A.E.H., K.L.L., L.A.C.), Boston University School of Public Health, Boston, MA; Center for Human Genetic Research (T.G., J.S.M., J.F.G., M.E.M.), Massachusetts General Hospital, Harvard Medical School, Boston; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.-P.V.), The Department of Pathology and Cell Biology, Columbia University Medical...
- Venue
- Neurology
- Published
- 2012-10-16
- Volume
- 79
- Issue
- 16
- Pages
- 1708-1715
- ISSN
- 0028-3878
- 1526-632X
- Cited by
- 46
- References
- 0
- Language
- en
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- Hadzi, T. C., Hendricks, A. E., Latourelle, J. C., Lunetta, K. L., Cupples, L. A., Gillis, T., Mysore, J. S., Gusella, J. F., MacDonald, M. E., Myers, R. H., & Vonsattel, J.-P. (2012). Assessment of cortical and striatal involvement in 523 Huntington disease brains. Neurology. https://doi.org/10.1212/wnl.0b013e31826e9a5d
