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Tau aggregate replication occurs at the pre-synapse of cultured human neurons and increases with application of TNFa

Tau aggregation at synapses is a key process driving Alzheimer's disease but the mechanism(s) that cause this have not been established. We used a model system of forward-programming induced glutamatergic neurons (iNeurons) with three independent cell lines treated with TNFa. Using aggregate-specific SIMOA, STED microscopy, and SynPull to detect nanoscopic tau aggregates in bulk samples and at individual synapses, we found that TNFa-driven tau aggregation occurs preferentially at the...

bioRxiv 7d ago