Jhodi M. Webster, Ya-Ting Yang, Aidan T. Miller, Asta Zane, Kasandra Scholz, William J. Stone, Nikhita Mudium, Nicole J. Corbin-Stein, Woong-Jai Won, Anna C. Stoll, Kelsey M. Greathouse, Noelle H. Cooper, Lillian F. Long, Phaedra N. Manuel, Jeremy H. Herskowitz, Talene A. Yacoubian, Daniel J. Tyrrell, Ivette M. Sandoval, Fredric P. Manfredsson, Jeffrey H. Kordower, Ashley S. Harms
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.