D-Ribosylated Tau forms globular aggregates with high cytotoxicity.

Although the glycation of Tau that is involved in paired helical filament formation in Alzheimer's disease has been widely studied, little attention has been paid to the role of D-ribose in the glycation of Tau. Here, we show that Tau is rapidly glycated in the presence of D-ribose, resulting in oligomerization and polymerization. Glycated derivatives appeared after 24 h incubation. Western blotting indicated the formation of advanced glycation end-products (AGEs) during initial stages of glycation. Thioflavin T-positive (ThT-positive) aggregations that appeared from day 4 indicated the globular-like features. Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globular-like. Kinetic studies suggested that D-ribosylated Tau is slowly oligomerized and rapidly polymerized with ThT-positive features. Moreover, D-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis. This work has demonstrated that D-ribose reacted with Tau protein rapidly, producing ThT-positive aggregations which had high cytotoxicity.