Taken together, our observations broaden the impact of soluble pathogenic tau released extracellularly and suggest that in addition to mediating trans-neuronal propagation of tau, pathogenic tau may also propagate tau pathology to brain microvascular endothelial cells, thereby contributing to the genesis of vascular dysfunction in Alzheimer’s disease and other tauopathies. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.