Anatomical characterization of pTau217 in sporadic AD: Revealing seeding and neurodegeneration within higher‐order cortical circuits

These data provide the first direct evidence of early-stage, soluble pT217-tau aggregating on the microtubules and interfering with endosomal trafficking, appearing to be toxic to dendritic integrity and neuronal function. Furthermore, we find evidence of pT217-tau trafficking between neurons near synapses to "seed" tau pathology in higher brain circuits, interfacing with the extracellular space to become accessible to CSF and blood. The expression of pT217-tau in dendrites with early signs of degeneration may help to explain why this tau species can herald future disease.