Next, we investigated whether the uptake of K18 PFFs is actin-dependent by inhibiting actin polymerization using Latrunculin A (32). Treatment with Latrunculin A resulted in a dose-dependent reduction in dextran uptake, a bona fide marker for actin-dependent fluid-phase endocytosis. With respect to K18 PFFs uptake and tau aggregation, actin polymerization inhibition clearly resulted in a significant reduction of internalized K18 PFFs (IC 50 = 57 nM) and consequently decreased significantly K18 PFFs-seeded tau aggregation (IC 50 = 25 nM) (Fig. 1, G and H). These **data** contradict previous reports that claim that tau aggregates are internalized by an actin-independent mechanism in iPSC-derived neurons (18), but support **data** from other cell lines (16). Overall, these **data** give further support, but now in primary hippocampal neurons, that internalization of K18 PFFs is governed by a clathrin-independent, but dynamin1-and actin-dependent mechanism. Importantly, we now also link a reduced amount of tau seeds internalization to decreased tau seeding in neurons.