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Identification of N-glycosylation changes in the CSF and serum in patients with schizophrenia.

Abstract:
Schizophrenia is a major neuropsychiatric disorder that affects 2% of the population worldwide. No biochemical diagnostic tests are available, and patients must undergo lengthy clinical evaluation periods before an accurate diagnosis can be given. Blood and cerebrospinal fluid are candidates for the identification of potential biomarkers for this disease. We have identified several N-glycans that distinguish first onset, unmedicated schizophrenia patients from healthy individuals. This is the first report of the N-glycome from low abundance serum proteins and cerebrospinal fluid. The tetraantennary tetrasialylated glycan with a polylactosamine extension, A4G4LacS4, from low abundance serum proteins showed a 2-fold increase in serum from male schizophrenia patients. Gender specificity was also demonstrated as the triantennary trisialylated glycan containing the SLex epitope was increased significantly in male schizophrenia patients on both high and low abundance serum proteins. Levels of bisecting and sialylated glycans in the cerebrospinal fluid showed a general down-regulation in schizophrenia patients and a 95% positive predictive power for distinguishing patients from controls. These changes are consistent with the reported down-regulation of beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase III and beta-galactoside alpha-2,3/6-sialyltransferases in the prefrontal cortex from schizophrenia patients. These alterations in the N-glycosylation signature could be used potentially for early diagnosis and monitoring of patients after treatment.

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Publisher copy:
10.1021/pr1002356

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Journal:
Journal of proteome research More from this journal
Volume:
9
Issue:
9
Pages:
4476-4489
Publication date:
2010-09-01
DOI:
EISSN:
1535-3907
ISSN:
1535-3893


Language:
English
Keywords:
Pubs id:
pubs:222842
UUID:
uuid:1b9e8f33-3d03-42ee-b4d3-097fd907b7b8
Local pid:
pubs:222842
Source identifiers:
222842
Deposit date:
2012-12-19
ARK identifier:

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