Hence, the clinical outcomes were similar for both types of NPs (with or without brain targeting ligand).[161] Nevertheless, NPs with small sizes (70 nm) with brain targeting ligands could invoke superior therapeutic effects due to crossing the BL, glia limitans and distribution in brain parenchyma.[176] It should be noted that expression of TfR decreases in the hippocampus of patients with AD compared to age‐matched controls.[177] Therefore, NP uptake may be affected in AD when NPs utilize transferrin mediated transport across the BBB. This evidence concerns the gene TF and Alzheimer disease.