Brain-specific proteins decline in the cerebrospinal fluid of humans with Huntington disease.
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.
Fang
Qiaojun
Q
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Strand
Andrew
A
Law
Wendy
W
Faca
Vitor M
VM
Fitzgibbon
Matthew P
MP
Hamel
Nathalie
N
Houle
Benoit
B
Liu
Xin
X
May
Damon H
DH
Poschmann
Gereon
G
Roy
Line
L
Stühler
Kai
K
Ying
Wantao
W
Zhang
Jiyang
J
Zheng
Zhaobin
Z
Bergeron
John J M
JJ
Hanash
Sam
S
He
Fuchu
F
Leavitt
Blair R
BR
Meyer
Helmut E
HE
Qian
Xiaohong
X
McIntosh
Martin W
MW
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
D002556:Cerebrospinal Fluid Proteins