Seeding human tau knock‐in neurons with human derived pathological tau results in the formation of pathogenic conformations of tau

One of the pathological hallmarks of Alzheimer’s disease (AD) is the accumulation of pathological tau inclusions. Conformational exposure of an N‐terminal motif in tau known as the phosphatase‐activating domain (PAD) occurs early in AD and other tauopathies and aberrant exposure of this motif disrupts axonal transport. Tau is capable of seeding aggregation in cells; however, the extent to which disease‐associated pathogenic conformations can be effectively seeded remains an area of active investigation. To help address this gap, we seeded aggregation in primary neurons and assessed known pathogenic tau conformations.