The aggregation of tau is observed across several neurodegenerative diseases classified as tauopathies. While tau has been studied extensively for several decades, little is known about the molecular mechanisms driving tau aggregation. One possible mechanism is the formation of cytoplasmic speckles, assemblies of mislocalized nuclear speckle proteins that contain polyserine domains, which creates a preferred site of tau aggregation. However, the nature of the interaction between tau and these polyserine containing assemblies, and the impact on developing tau pathology, are unknown. My goal was to characterize the nature and consequence of tau-polyserine interactions, leading to a mechanistic understanding of tau aggregation with polyserine. Specifically, I performed a series of in vitro experiments with recombinant proteins and cell culture models to characterize the tau-polyserine interaction. I found that polyserine is capable of self-assembly, and that these assemblies interact directly with tau. This interaction increases the rate of formation and growth of seeding competent tau fibers. In cells, I found that polyserine-rich domains can enrich in tau aggregates independent of exacerbating tau aggregation. I used a series of separation of function polyserine variants to show that polyserine assembly and polyserine targeting to tau aggregates are distinct functions. Using a polyserine fusion protein that blocks polyserine self-assembly in cells, I show that polyserine assembly is necessary for increasing tau aggregation. I also briefly discuss how the SARS-CoV-2 pandemic may result in increased diagnoses of tauopathies. I summarize previous viral pandemics and how they lead to tauopathy sequelae and propose a mechanism in which viral infection triggers neuroinflammation and tau aggregation.