O-linked N-acetylglucosamine is upregulated in Alzheimer brains.

We present evidence that the expression of the novel intracellular carbohydrate modification of proteins--O-glycosidically linked N-acetylglucosamine (O-GlcNAc)--is significantly upregulated in Alzheimer brains over that of age matched control brains. This increase is specific for proteins associated with the detergent insoluble cytoskeleton and not for proteins of the detergent soluble fraction and is not due to an increase in protein expression in this fraction. The possible involvement of abnormal phosphorylation in the disease state and the interplay between phosphorylation and the O-GlcNAc modification suggests that the increased level of intracellular O-GlcNAc expression may be implicated in the pathogenesis of Alzheimer's disease.