Tau prions in AD and CTE contain both 3R and 4R tau isoforms. Tau prions were isolated using sodium PTA from control, PiD, AD, CTE, AGD, CBD, and PSP patient samples and were then incubated with Tau(3RD*VM,4RD*LM)–YFP cells for 4 d. Tau(3RD*VM,4RD*LM)–YFP cells express both the 3R and 4R repeat domains of tau with mutations L266V and V337M (3RD) and P301L and V337M (4RD). (A) Quantification of cell infection using control (n = 6), PiD (n = 6), AD (n = 7), CTE (n = 5), AGD (n = 2), CBD (n = 5), and PSP (n = 6) patient samples was determined by standardizing the total fluorescence in each image to the total cell count. Prions from all six tauopathies, including AD and CTE, infected the Tau(3RD*VM,4RD*LM)–YFP cells, whereas the control samples showed no infection (PiD, P = 0.07; AD, P = 0.05; CTE, P < 0.001; AGD, P < 0.01; CBD, P < 0.001; PSP, P < 0.001). *P < 0.01. Data are shown as the mean from five images per well in six wells. All values are shown in Table S2. (B) Representative images of HEK293T cells infected with PiD, AD, CTE, AGD, CBD, and PSP but not control patient samples. YFP is shown in green. (Scale bar, 50 μm.)