Vol. 9, Issue 12, Part G (2025)

Rab GTPases are central regulators of vesicle trafficking, and their dysregulation is increasingly linked to the pathogenesis of Alzheimer’s disease (AD). To understand how tau-mediated cellular stress affects endosomal dynamics, we employed an okadaic acid (OA)-induced tau hyperphosphorylation model in Neuro2A cells. Cells were treated with OA (100 nM, 4 h), and the expression of Rab5, Rab7, Rab9, and Rab11 was assessed by Western blotting followed by densitometric analysis. OA-induced tau hyperphosphorylation resulted in a marked reduction of Rab5, an essential early endosomal marker, indicating impaired early vesicle sorting. Rab7, which mediates the maturation of Rab5-positive endosomes into late endosomes, was also decreased, suggesting a disruption in endosomal progression. In contrast, Rab9, a late endosomal marker associated with trafficking to the trans-Golgi network, showed elevated expression upon OA exposure, consistent with a shift toward late endosomal accumulation. Rab11, which governs recycling endosome function, exhibited altered expression patterns indicative of impaired recycling pathways under tau-driven stress. Together, these findings suggest that tau hyperphosphorylation perturbs the balance of early, late, and recycling endosomal trafficking, potentially contributing to vesicular dysfunction observed in AD. Further mechanistic studies are needed to elucidate how Rab dysregulation integrates into tau-mediated neurodegenerative pathways.