Tracking of in vivo O-GlcNAcylation in an Alzheimer's Disease and Aging C. elegans Model

We investigated O-linked {beta}-N-acetylglucosamine (O-GlcNAc), a post-translational modification, in an in vivo Caenorhabditis elegans model of Alzheimers Disease and aging. Employing a chemoenzymatic labeling strategy combined with an automated image processing approach, we analyzed both post-hatching and adult stages of wild-type N2 and transgenic strain expressing human tau V337M under the aex-3 promoter (aex-3p::tau(V337M)). Labeled O-GlcNAc proteins were visualized using fluorescence microscopy and quantified using a region-of-interest-based image analysis pipeline. Morphometric characterization revealed an age-dependent increase in O-GlcNAcylation in wild-type worms, while the AD model showed a progressive decline. In middle-aged transgenic nematodes, O-GlcNAc-labeled regions of interest shifted from anterograde to predominantly retrograde movement, suggesting that aging and neurodegeneration alter O-GlcNAc trafficking dynamics, potentially reflecting impaired synaptic support or enhanced clearance in C. elegans. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/659071v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@10d6816org.highwire.dtl.DTLVardef@12ca2d8org.highwire.dtl.DTLVardef@17742b2org.highwire.dtl.DTLVardef@bbc33b_HPS_FORMAT_FIGEXP M_FIG C_FIG