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Updated: Jun 5, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
O-GlcNAcylation increases non-amyloidogenic processing of the amyloid-β precursor protein (APP)
Kristin T Jacobsen1, Kerstin Iverfeldt
1Department of Neurochemistry, Stockholm University, SE-10691 Stockholm, Sweden.
Abstract:
The amyloid-β precursor protein (APP) was shown to be O-GlcNAcylated 15 years ago, but the effect of this modification on APP processing and formation of the Alzheimer's disease associated amyloid-β (Aβ) peptide has so far not been investigated. Here, we demonstrate with pharmacological tools or siRNA that O-GlcNAcase and O-GlcNAc transferase regulate the level of O-GlcNAcylated APP. We also show that O-GlcNAcylation increases non-amyloidogenic α-secretase processing, resulting in increased levels of the neuroprotective sAPPα fragment and decreased Aβ secretion. Our results implicate O-GlcNAcylation as a potential therapeutic target for Alzheimer's disease.
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