TFRC and Alzheimer disease: These barriers maintain CNS homeostasis by limiting the circulation of molecules from peripheral circulation.95 Among these barriers, blood–brain-barrier (BBB) is the most stringent one allowing only 0.1–0.2 % of circulating antibodies to the brain.96, 97 While there is a controversy over whether or not the BBB is compromised in AD patients, novel techniques have risen to enhance antibody delivery into the CNS such as taking advantage of transferrin receptor (TfR)98–100 intranasal delivery,101 and others.