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Molecular & Cellular Proteomics 8:451-466, 2009.
© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease^*,S

Qiaojun Fang, Andrew Strand, Wendy Law, Vitor M. Faca, Matthew P. Fitzgibbon, Nathalie Hamel^¶, Benoit Houle^¶, Xin Liu^||, Damon H. May, Gereon Poschmann^**, Line Roy^¶, Kai Stühler^**, Wantao Ying^||, Jiyang Zhang^||, Zhaobin Zheng^||, John J. M. Bergeron^¶, Sam Hanash, Fuchu He^||, Blair R. Leavitt, Helmut E. Meyer^**, Xiaohong Qian^|| and Martin W. McIntosh^,

From the Public Health Sciences Division and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, ^¶ Department of Anatomy and Cell Biology, McGill University, Quebec H3A 1A4, Canada, ^|| State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing 102206, China, ^** Medizinisches Proteom-Center, Ruhr-Universität Bochum, D-447801 Bochum, Germany, and Department of Medical Genetics, University of British Columbia and Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada

We integrated five sets of proteomics data profiling the constituents of cerebrospinal fluid (CSF) derived from Huntington disease (HD)-affected and -unaffected individuals with genomics data profiling various human and mouse tissues, including the human HD brain. Based on an integrated analysis, we found that brain-specific proteins are 1.8 times more likely to be observed in CSF than in plasma, that brain-specific proteins tend to decrease in HD CSF compared with unaffected CSF, and that 81% of brain-specific proteins have quantitative changes concordant with transcriptional changes identified in different regions of HD brain. The proteins found to increase in HD CSF tend to be liver-associated. These protein changes are consistent with neurodegeneration, microgliosis, and astrocytosis known to occur in HD. We also discuss concordance between laboratories and find that ratios of individual proteins can vary greatly, but the overall trends with respect to brain or liver specificity were consistent. Concordance is highest between the two laboratories observing the largest numbers of proteins.

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