Identification of N-Glycosylation Changes in the CSF and Serum in Patients with Schizophrenia

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• 作者：Johannes L. Stanta ; Radka Saldova ; Weston B. Struwe ; Jennifer C. Byrne ; F. Markus Leweke ; Matthius Rothermund ; Hassan Rahmoune ; Yishai Levin ; Paul C. Guest ; Sabine Bahn ; Pauline M. Rudd
• 刊名：Journal of Proteome Research
• 出版年：2010
• 出版时间：September 3, 2010
• 年：2010
• 卷：9
• 期：9
• 页码：4476-4489
• 全文大小：588K
• 年卷期：v.9,no.9(September 3, 2010)
• ISSN：1535-3907

文摘

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 SLe^x 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 β-1,4-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase III and β-galactoside α-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.

Keywords:

human plasma glycome; human CSF glycome; glycosylation in schizophrenia; biomarker; cerebrospinal fluid; CSF; depleted serum; N-linked glycans; diagnostic