First, tau causes NO problem

Pathological tau disrupts the association between nitric oxide (NO) synthase and PSD95, impairing NO signaling and neurovascular coupling before causing neurodegeneration. Stopping production of pathological tau rescues NO signaling, neurovascular coupling and neuronal function, but doesn’t remove tangles, suggesting that (like amyloid-ß) soluble tau is an important driver of early neurovascular dysfunction and subsequent neuronal damage.