VPS35 retromer dysfunction accelerates tau spread by impairing retrograde endosomal trafficking, increasing the pool of tau available for trans-synaptic transfer. Retromer stabilizing compounds that enforce the VPS35/26/29 trimer could break the propagation cycle. This is a high-leverage mechanism because it targets the spreading step rather than tau synthesis or aggregation per se, potentially acting at all disease stages. Falsifiable prediction: R55 retromer stabilizer (10 mg/kg i.p., daily) starting 2 weeks post-hippocampal PS19 tau-seed injection should reduce tau immunoreactivity in connected entorhinal cortex and amygdala by ≥60% vs vehicle at 4 months post-injection (AT8 IHC; blind scoring). Microfluidic chamber tau-seeding assay: VPS35 activator should reduce tau transmission from axon→soma compartment by ≥70%.