RI-OR2-TAT is a brain-penetrable inhibitor targeting β-amyloid (β-Amyloid) oligomerization. It is engineered by integrating the HIV protein transduction domain TAT into RI-OR2. RI-OR2-TAT binds to Aβ42 fibrils with a Kd value of 58-125 nM. It reduces Aβ aggregation and plaque levels, diminishes microglial activation and oxidative damage, and enhances the number of young neurons in the dentate gyrus.