Thus, key to understanding the potential role of LRP1s in tau propagation across cells is whether LRP1 mediates, either directly or indirectly, the uptake of human brain–derived tau from patients with AD and facilitates escape from endosomal/lysosomal systems, providing misfolded tau access to the cytoplasm to lead to seeding of endogenous tau. Here, LRP1 is linked to Alzheimer disease.