Parkinson’s disease is characterized by the accumulation of the protein alpha-synuclein within the neuronal cytoplasm. These pathological aggregates are toxic to neurons and are released upon their cell death. Interestingly, recent evidence has indicated co-aggregation of alpha-synuclein with the Alzheimer’s-associated protein Tau. This co-aggregation correlates with faster disease progression and more severe Parkinson’s symptoms.Microglia are the resident innate immune cells of the brain. They are the first line of immune defense and responsible for the removal of cytotoxic protein aggregates. Microglia phagocytose and break down accumulating alpha-synuclein complexes to reduce disease progression.Here, we study how the co-aggregation of alpha-synuclein along with Tau affects its clearance by microglia. We show that alpha-synuclein pre-formed fibrils form co-aggregates with Tau pre-formed fibrils in vitro. Primary murine microglia subjected to these co-aggregates show less efficient phagocytosis of alpha-synuclein protein compared to the administration of alpha-synuclein alone. Furthermore, microglial degradation of alpha-synuclein alleviate in the presence of Tau aggregates. In addition, microglia exhibit heightened responsiveness to co-aggregates, as evidenced by their increased cytokine release in comparison to alpha-synuclein alone. In summary, our findings could elucidate the accelerated progression of Parkinson's disease in individuals concurrently experiencing Tau aggregation.