title: CSF N-glycoproteomics for early diagnosis in Alzheimer's disease.
abstract: This work aims at exploring the human CSF (Cerebrospinal fluid) N-glycome by MALDI MS techniques, in order to assess specific glycosylation pattern(s) in patients with Alzheimer's disease (n:24) and in subjects with mild cognitive impairment (MCI) (n:11), these last as potential AD patients at a pre-dementia stage. For comparison, 21 healthy controls were studied. We identified a group of AD and MCI subjects (about 40-50% of the studied sample) showing significant alteration of CSF N-glycome profiling, consisting of a decrease in the overall sialylation degree and an increase in species bearing bisecting GlcNAc. Noteworthy, all the MCI patients that converted to AD within the clinical follow-up, had an abnormal CSF glycosylation profile. Based on the studied cohort, CSF glycosylation changes may occur before an AD clinical onset. Previous studies specifically focused on the key role of glycosyltransferase GnT-III on AD-pathogenesis, addressing the patho-mechanism to specific sugar modification of BACE-1 glycoprotein with bisecting GlcNAc. Our patients addressed protein N-glycosylation changes at an early phase of the whole biomolecular misregulation on AD, pointing to CSF N-glycome analyses as promising tool to enhance early detection of AD and also suggesting alternative therapeutics target molecules, such as specific glyco-enzymes.
authors.affiliation: Institute for Polymers, Composites and Biomaterials-CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Palmigiano
authors.affiliation: Institute for Polymers, Composites and Biomaterials-CNR, Via P. Gaifami 18, 95126 Catania, Italy; Child Neurology and Psychiatry, Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95125 Catania, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Barone
authors.affiliation: Institute for Polymers, Composites and Biomaterials-CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Sturiale
authors.affiliation: Section of Neurosciences-Dept. GF Ingrassia, University of Catania, Via S. Sofia 78, 95125 Catania, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sanfilippo
authors.affiliation: Institute for Polymers, Composites and Biomaterials-CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Rosaria Ornella
authors.initials: RO
authors.lastname: Bua
authors.affiliation: Institute for Polymers, Composites and Biomaterials-CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Donata Agata
authors.initials: DA
authors.lastname: Romeo
authors.affiliation: Institute for Polymers, Composites and Biomaterials-CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Messina
authors.affiliation: Section of Neurosciences-Dept. GF Ingrassia, University of Catania, Via S. Sofia 78, 95125 Catania, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Capuana
authors.affiliation: Section of Neurosciences-Dept. GF Ingrassia, University of Catania, Via S. Sofia 78, 95125 Catania, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Maci
authors.affiliation: Section of Neurosciences-Dept. GF Ingrassia, University of Catania, Via S. Sofia 78, 95125 Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Le Pira
authors.affiliation: Section of Neurosciences-Dept. GF Ingrassia, University of Catania, Via S. Sofia 78, 95125 Catania, Italy. Electronic address: m.zappia@unict.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Zappia
authors.affiliation: Institute for Polymers, Composites and Biomaterials-CNR, Via P. Gaifami 18, 95126 Catania, Italy. Electronic address: domenico.garozzo@unict.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Garozzo
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D042241:Early Diagnosis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006023:Glycoproteins / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D020543:Proteome / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D020543:Proteome
keywords: Alzheimer's disease; Bisected glycans; Early diagnosis; MGAT3; Mild cognitive impairment; N-glycomics