Tau, amyloid-β and α-synuclein co-pathologies synergistically enhance neuroinflammation and hippocampal neuron loss

microglia, a population of activated, phagocytosing microglia, compared to single pathologies. These changes were abundant in the hippocampus and cortex, regions that showed elevated protein pathology load at 3- and 6-months post-induction and enhanced neuronal loss at 6-months post induction. Our findings demonstrate that co-pathologies promote accumulation of proteinopathy and synergistically enhance immune activation in the hippocampus and cortex and hippocampal neuronal loss. With this model as a novel tool to assess mixed-pathology mechanisms, our results support the need for combinatorial therapeutic strategies, that target both co-pathologies and inflammation, and identifies neuroinflammation as a prominent feature associated with co-pathology enhanced neurodegeneration.