Reduction of O-linked N-acetylglucosamine-modified assembly protein-3 in Alzheimer's disease

Pamela J. Yao, Paul D. Coleman

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

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 neurofibriliary tangles. These data suggest a possible association between the O-glycosylated AP-3 and AD pathology.

Original languageEnglish (US)
Pages (from-to)2399-2411
Number of pages13
JournalJournal of Neuroscience
Volume18
Issue number7
DOIs
StatePublished - Apr 1 1998
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Clathrin assembly protein AP-3
  • Galatosyltransferase labeling
  • N-acetylglucosamine
  • Neurofibrillary tangles
  • O-linked glycosylation
  • Phosphorylation

ASJC Scopus subject areas

  • General Neuroscience

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