Identification of N-Glycosylation in the CSF in Patients with Alzheimer's disease by MALDI Mass Spectrometry

Neurodegenerative diseases are defined as hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral structures of the nervous system. They include diseases such as Alzheimer's Disease and other dementias, Brain Cancer, Degenerative Nerve Diseases, Encephalitis, Epilepsy, Genetic Brain Disorders, Head and Brain Malformations, Hydrocephalus, Stroke, Parkinson's Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease), Huntington's Disease, Prion Diseases, Creutzfeld-Jakob disease (CJD) and others. The prevalence of neurodegenerative disorders is increasing, but diagnostic biomarkers and effective treatments are lacking. Cerebrospinal fluid (CSF) is produced from the choroid plexus within the ventricles of the brain and circulates through the ventricular system and around the outside of brain; because its composition is rapidly and directly influenced by the brain, CSF represents an appealing source for diagnostic biomarkers. Glycosylation is one of the most common and most complex post-translational modifications (PTMs) of secreted and cell surface proteins and plays a critical role in protein-protein, protein-cell, and cell-cell interactions including antibody binding, protein degradation, cellular endocytosis, and protease protection. Glycosylation is cell-type specific and reproducible for a given physiological state. Glycoproteins occur usually as a collection of glycoforms that differ in the structure of the component oligosaccharides. Glycoform abundance and glycan structures can be altered significantly in disease, resulting in a characteristic signature as a means of investigating complex pathophysiological processes and revealing novel biomarkers and drug targets. Here we describe a promising strategy for discovering N-glycan biomarkers in individual CSF in patients with neurodegenerative diseases based on analyzing total glycan profiles rather than the sugars on particular glycoproteins.