title: Lectin-affinity chromatography brain glycoproteomics and Alzheimer disease: insights into protein alterations consistent with the pathology and progression of this dementing disorder.
abstract: Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of senile plaques and neurofibrillary tangles, and both these pathological hallmarks of AD are extensively modified by glycosylation. Mounting evidence shows that alterations in glycosylation patterns influence the pathogenesis and progression of AD, but the vast number of glycan motifs and potential glycosylation sites of glycoproteins has made the field of glycobiology difficult. However, the advent of glycoproteomics has produced major strides in glycoprotein identification and glycosylation site mapping. The use of lectins, proteins that have strong affinity for specific carbohydrate epitopes, to enrich glycoprotein fractions coupled with modern MS, have yielded techniques to elucidate the glycoproteome in AD. Proteomic studies have identified brain proteins in AD and arguably the earliest form of AD, mild cognitive impairment, with altered affinity for Concanavalin-A and wheat germ agglutinin lectins that are consistent with the pathology and progression of this disorder. This is a relatively nascent field of proteomics research in brain, so future studies of lectin-based brain protein separations may lead to additional insights into AD pathogenesis and progression.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA. dabcns@uky.edu
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Owen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002846:Chromatography, Affinity; D003072:Cognition Disorders / Q000378:metabolism; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods
chemical_list: D006023:Glycoproteins; D037102:Lectins