CLU and supranuclear palsy, progressive, 1: In this study, we demonstrate that (1) tau accumulates within synaptic pairs in PSP, (2) pathological tau colocalizes with synaptogyrin-3 in presynapses, (3) astrocytes show increased synaptic engulfment in PSP, (4) clusterin is close enough to bind tau within human synapses and (5) PSP-derived tau can be taken up into postsynapses and induce astrogliosis and augmented synaptic engulfment in living HBSCs.