RI-OR2-TAT is a brain-penetrant inhibitor of β-Amyloid oligomerization, which is produced by adding the HIV protein transduction domain TAT to RI-OR2. RI-OR2-TAT binds to Aβ42 fibrils with a K d value of 58-125 nM. RI-OR2-TAT reduces Aβ aggregation and plaque levels, reduces activation of microglia and oxidative damage, and increases the number of young neurons in the dentate gyrus.