Seeding Alzheimer's disease-associated tau pathology in MAPT knock-in primary neurons causes early axonopathy and synaptic dysfunction.

ABSTRACT: The progressive accumulation of pathological tau is a hallmark of Alzheimer's disease (AD). The bulk of existing in vitro and in vivo evidence suggests that pathological tau forms can seed further aggregation of the protein. However, many of the subsequent functional consequences following the formation of pathogenic tau aggregates are not yet fully understood. Here, we utilized the tau seeding phenomenon to induce the formation of pathogenic tau and identify intracellular consequences in a neuron culture model of AD-associated tauopathy. Primary neurons from human tau knock-in (MAPT-KI) mice were seeded with human AD brain-derived insoluble tau (AD-tau). Microscopy and biochemical assays were used to characterize the pathological tau species formed, as well as the extent of neuronal, axon

SUBMITTER: Mueller RL 

PROVIDER: S-EPMC12578843 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature