Although it is difficult to determine whether the increase in a-syn and tau pathologies in this model is also mediated by Ab, the results clearly support the notion that Ab, tau and a-syn promote the aggregation of each other. In this study, we confirm and extend these observations in various neuronal models of synucleinopathy. The tau-induced increase in the number of aggregates and HMW species of a-syn observed in our study provides evidence that tau synergistically affects the polymerization of a-syn. In particular, tau increased the levels of insoluble syn-T rather than affecting total levels. A possible explanation for the increase in the insoluble syn-T fraction is the ability of tau to inhibit histone deacetylase 6, a key component of the aggresome complex. This inhibitory effect of tau on HDAC6 could affect the transport of small aggregates to aggresomes or the assembly into larger aggregates. In addition, our observation that co-expression of tau leads to smaller a-syn inclusions and enhanced toxicity may suggest that microaggregates are one of the key factors that mediate toxicity in our model. This is consistent with studies that show a massive presence of small aggregates in presynaptic terminals associated with loss of dendritic spines in the brains of patients with DLB. Taken together, these results support the idea that microaggregates, rather than LBs, likely represent the pathogenic component that drive neurodegeneration in ABT-199 in vivo synucleinopathies. The increase in a-syn HMW species in the presence of tau in our study also provides evidence for a central role of soluble oligomers in DLB and other synucleinopathies. It is tempting to speculate that, in the presence of tau, these microaggregates may drive dendritic and synaptic damage by slowly releasing oligomeric forms of a-syn. Different studies have identified that monomeric and oligomeric a-syn are secreted to the extracellular medium from neuronal cells via exocytosis. These findings provide strong evidence for direct cell-to-cell propagation of asyn, similar to that observed in prion diseases. Here, we detected an increase in a-syn secretion when tau was overexpressed. Although we cannot completely rule out that the increase in extracellular a-syn levels in the presence of tau is due to membrane leakage, the large increase observed compared to the slight toxicity argues against this possibility. Instead, this suggests that a-syn secretion might be triggered by the toxic properties of overexpressed a-syn and that tau specifically enhances a-syn secretion. This tau-enhanced secretion of a-syn may be relevant in cases with a cooccurrence of a-syn and tau pathologies, such as our earlyonset DLB family. Together, our data reinforce the notion that synergistic effects between a-syn and tau may be a relevant disease component that enhances the pathological cascade and spreads the damage in neurodegenerative diseases that show co-occurrence of both pathologies. Water-borne transmission of influenza A viruses has been suggested as an important transmission mechanism in wild and domestic duck populations.