Vector production and titration were performed as previously described43. Briefly, each pAAV plasmid was co-transfected with the pDP6 helper plasmid in HEK293-AAV cells (Agilent Technologies). Transfected cells were lysed 48 h later by freeze-thaw cycles. Recovered viral particles were sequentially purified on iodixanol density gradients and heparin affinity columns. Infectivity titers were determined according to the amount of TU measured by real-time PCR, at 48 h after infection of HEK293T cells. The titers obtained for each AAV2/6 vector suspension were: 1.88E + 10 TU/ml, 1.87E + 10 TU/ml and 6.75E + 10 TU/ml for WT 4R0N tau (3 batches); 5.79E + 10 TU/ml and 5.24E + 10 TU/ml for P301S mutant 4R0N tau (2 batches); 2.43E + 10 TU/ml for 2P mutant 4R0N tau.