Our neuropathological data suggest that tau pathology rather uniformly emergesfirst in neurons in the pallido-nigro-luysian system in PSP patients, with clinical subtypesbeing distinguished by distinct downstream tau spreading patterns along differentcircuits.2 This concept issupported by our most recent observation that tau pathology in PSP appears indeed to spreadalong neuronal connectivity pathways.6 It remains to be elucidated prospectively which factors predispose for thespreading routes occurring in individual patients, thereby leading to different clinical PSPvariants. The gene discussed is MAPT; the disease is supranuclear palsy, progressive, 1.