Glycoproteomics as an Emerging Tool for Medicinal Biology and Biomarker Development: A case study of cognitive decline in diabetic patients
2The Joseph Sagol Neuroscience Center, Sheba Medical Center, Israel
3G-INCPM, The Weizmann Institute of Science, Israel
4School of Psychology, Reichman University, Israel
5Department of Medicine, The Icahn School of Medicine at Mount Sinai, USA
6Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, USA
7Department of Neuroscience, Rush University, USA
Protein glycosylation is a crucial modification for the correct function of cellular systems. Glycosylation is involved in protein-protein interaction, cell-cell interaction, the correct growth of the extracellular matrix and is an important target for virulence factors for cellular infection and penetration. Changes in glycan synthesis are observed in severe diseases such as CDGs (Cognitive Disorders of Glycosylation), cancer, autoimmunity and inflammation, diabetes and others.
Here we present a novel platform for quantitative glycoproteomics, and demonstrate its utility in analysis of clinical samples from cognitive-impaired versus non impaired, elderly, diabetic patients. Our method identifies the glycan composition and the site on the protein simultaneously for N-linked, O-linked and glycation. An analysis of 69 serum samples resulted in multiple differentially expressed glycopeptides in cognitive-impaired patients that point to changes in the glycan synthetic pathways, protein maturation and discuss implications for protein function.
Using our platform, we investigate the serum glycoproteome of diabetic patients, and show that 137 different glycopeptides are differentially quantified between patients with cognitive decline vs those without. These findings demonstrate our ability to capture a large portion of the glycoproteome is complex samples.