To further validate the effects of RAP‐RL on vascular normalization, we continued to determine the effect of RAP‐RL on the expression of the BBB tight‐junction proteins including claudin‐5 and ZO‐1, which were significantly altered under AD.[31] Consistent with that found in bEnd.3 cells, in 13‐month‐old male APP/PS1 mice, RAP‐RL significantly increased claudin‐5 density (by 78.24%) comparing with the vehicle control (Figure 5e,f). The gene discussed is TJP1; the disease is Alzheimer disease.