Reduction of O-linked N-acetylglucosamine-modified assembly protein-3 in Alzheimer's disease.
Abnormal protein processing and modification is associated with Alzheimer's disease (AD) pathology. The role of phosphorylation in AD has been studied extensively because the presumed abnormal phosphorylation of tau protein is believed to play a role in the formation of paired helical filaments. Glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues is a dynamic protein modification of intracellular proteins, and it shares similar features with protein phosphorylation. In this study, O-GlcNAc glycosylation of proteins from autopsied human brains with confirmed AD and non-AD age-matched controls was examined. O-GlcNAcylation was demonstrated by labeling protein extracts with [3H]galactose in the presence of galactosyltransferase and subsequent analyses of saccharide-protein linkage and saccharide structure. The number of O-GlcNAc-containing proteins and the overall O-GlcNAc level do not appear to be different between AD and control brain tissues. The only significant change observed is a marked reduction of O-GlcNAcylated clathrin assembly protein-3 (AP-3) in AD. The reduction is more evident in brain neocortical regions, and there appears to be a negative correlation between O-glycosylated AP-3 and the density of neurofibrillary tangles. These data suggest a possible association between the O-glycosylated AP-3 and AD pathology.
Yao
P J
PJ
Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, New York 14642, USA.
Coleman
P D
PD
D000107:Acetylation; D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000737:chemistry / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000201:enzymology; D005690:Galactose; D005700:Galactosyltransferases / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009844:Oligosaccharides / Q000032:analysis / Q000378:metabolism; D010047:Ovalbumin / Q000032:analysis; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D014316:Tritium
D033942:Adaptor Proteins, Vesicular Transport; D004791:Enzyme Inhibitors; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D009844:Oligosaccharides; D010750:Phosphoproteins; C439023:clathrin assembly protein AP180; D014316:Tritium; D010047:Ovalbumin; D005700:Galactosyltransferases; D000117:Acetylglucosamine; D005690:Galactose