Taken together our observations suggest that soluble tau aggregate entry to endothelial cells mediates the accumulation of pathogenic tau in AD and in P301S(PS19) mice, and are consistent with prior studies that documented peripheral clearance of tau following anti-tau antibody administration in tauopathy patients and in mice modeling tauopathy, and showed that tau isoforms can cross the BBB23,24,60. Here, MAPT is linked to Alzheimer disease.