Fig. 3

Seeding activity detects spread of tau pathology. a Tau strains DS1, 9, and 10 have different inclusion morphologies. DS1 does not contain aggregated tau. DS9 cells feature nuclear speckles, while DS10 cells have a large juxtanuclear aggregate and no nuclear speckles. b Cell lysate from DS1, 9, or 10 was inoculated into the hippocampi of young PS19 mice. At 3, 6, or 12 weeks, brains were collected for tau histopathology and seeding analysis. c Inoculation of DS1 did not induce AT8 pathology. Mice inoculated with DS9 developed NFT-like AT8 pathology in CA1 of the ipsilateral hippocampus by three weeks. This pathology spread to the contralateral hippocampus by 6 weeks. DS10 produced limited tau pathology in this region. d DS9 inoculation induced neurofibrillary tangle-like pathology in CA3 of the ipsilateral hippocampus, and limited pathology in the contralateral hippocampus by six weeks. DS10 inoculation primarily induced mossy fiber AT8 pathology that progressed over time, and spread to the contralateral hippocampus by 12 weeks. e The percentage of the hippocampus covered with AT8 tau pathology was assessed in mice inoculated with DS1, 9, and 10 at each time point. Tau AT8 pathology and spread was apparent in DS9 inoculated mice. However, DS10 mossy fiber pathology was difficult to detect with this technique and showed variable pathology among animals (f). Tau seeding activity was detected in ipsilateral and contralateral hippocampi of DS9 and DS10 inoculated mice at 3 weeks. Seeding activity increased by 12 weeks, suggesting tau pathology continues to develop over time. ANOVA analysis was performed by comparing samples within each time point to DS1 inoculated controls. Error bars = S.E.M, * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001