title: Brain-specific proteins decline in the cerebrospinal fluid of humans with Huntington disease.
abstract: 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.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Fang
authors.forename: Andrew
authors.initials: A
authors.lastname: Strand
authors.forename: Wendy
authors.initials: W
authors.lastname: Law
authors.forename: Vitor M
authors.initials: VM
authors.lastname: Faca
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fitzgibbon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hamel
authors.forename: Benoit
authors.initials: B
authors.lastname: Houle
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Damon H
authors.initials: DH
authors.lastname: May
authors.forename: Gereon
authors.initials: G
authors.lastname: Poschmann
authors.forename: Line
authors.initials: L
authors.lastname: Roy
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
authors.forename: Wantao
authors.initials: W
authors.lastname: Ying
authors.forename: Jiyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhaobin
authors.initials: Z
authors.lastname: Zheng
authors.forename: John J M
authors.initials: JJ
authors.lastname: Bergeron
authors.forename: Sam
authors.initials: S
authors.lastname: Hanash
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Qian
authors.forename: Martin W
authors.initials: MW
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002556:Cerebrospinal Fluid Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D006816:Huntington Disease / Q000134:cerebrospinal fluid*; D007753:Laboratories; D051379:Mice; D009928:Organ Specificity; D040901:Proteomics
chemical_list: D002556:Cerebrospinal Fluid Proteins