Molecular & cellular proteomics : MCP · 2008
Brain-specific proteins decline in the cerebrospinal fluid of humans with Huntington disease.
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Fang Qiaojun, Strand Andrew, Law Wendy, Faca Vitor M, Fitzgibbon Matthew P, Hamel Nathalie, Houle Benoit, Liu Xin, May Damon H, Poschmann Gereon, Roy Line, Stühler Kai, Ying Wantao, Zhang Jiyang, Zheng Zhaobin, Bergeron John J M, Hanash Sam, He Fuchu, Leavitt Blair R, Meyer Helmut E, Qian Xiaohong, McIntosh Martin W
Аннотация
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.