Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state

Abstract Deposits of different abnormal forms tau in neurons and astrocytes represent key anatomo-pathological features tauopathies. Although protein is highly enriched poorly expressed by astrocytes, the origin astrocytic still elusive. Here, we used innovative gene transfer tools to model tauopathies adult mouse brains investigate tau. We showed our adeno-associated virus (AAV)-based models Thy-Tau22 transgenic mice that pathology can emerge secondarily neuronal pathology. By designing an vivo reporter system, further demonstrated bidirectional exchanges species between astrocytes. then determined consequences accumulation on their survival displaying various status aggregation. Using stereological counting report that, as for neurons, soluble are toxic some subpopulations hippocampus, whereas aggregates does not affect survival. Thus, mere bystanders Our results strongly suggest may significantly contribute clinical symptoms.