a, Immunoblot analysis and quantification of total tau in primary neurons after treatment with conditioned medium from primary wild-type microglia (control), LPS/ATP-activated wild-type, Asc- or Nlrp3-knockout microglia (wild type + ATP, Asc–/– + ATP or Nlrp3–/– + ATP). n = 4 for each group. Control versus wild type + ATP: *P = 0.0252, wild type + ATP versus Asc–/– + ATP: *P = 0.0148, wild type + ATP versus Nlrp3–/– + ATP: **P = 0.0029. b, IL-1β levels in conditioned medium of primary wild-type microglia primed with LPS and treated with hippocampus homogenate from either 11-month-old wild-type or Tau22 mice. n = 5 for primed, n = 4 for wild-type and Tau22 homogenate treated microglia. Primed versus Tau22: **P = 0.0092, wild type versus Tau22: *P = 0.0276. c, IL-1β levels in conditioned medium of primary wild-type, Asc–/– and Nlrp3–/– microglia primed with LPS and treated with different forms of 2 μM recombinant wild-type tau (tau WT). n = 3 for Asc–/– and Nlrp3–/– microglia treatments and wild-type oligomer treatment, n = 8 for all other wild-type treatments. Wild-type primed versus wild-type monomers: **P = 0.0011, wild-type primed versus wild-type oligomers: ***P = 0.0007, wild-type monomers versus Asc–/– and Nlrp3–/– monomers: **P = 0.0011, wild-type monomers versus wild-type fibrils: *P = 0.0388, wild-type oligomers versus Asc–/– and Nlrp3–/– oligomers: ***P = 0.0004, wild-type oligomers versus wild-type fibrils: *P = 0.0112. d, IL-1β levels in conditioned medium of primary wild-type, Asc–/– and Nlrp3–/– microglia primed with LPS and treated with different forms of 2 μM recombinant tau with a P301S (tau P301S) mutation. n = 8 for wild-type microglia treatments, n = 3 for Asc–/– and Nlrp3–/– microglia treatments, ***P = 0.0002, **P = 0.0018. e, IL-1β levels in conditioned medium of primary wild-type microglia primed with LPS and treated with different forms of 2 μM recombinant tau wild type with and without the NLRP3 inhibitior CRID3. n = 4 for all groups, ***P = 0.0002, ****P < 0.0001. f, IL-1β levels in conditioned medium of primary wild-type microglia primed with LPS and treated with different forms of 2 μM recombinant tau P301S with and without CRID3 treatment. n = 4 for all groups, **P = 0.0037, ***P = 0.0005, ****P < 0.0001. g, Jess-based analysis of conditioned medium of LPS + tau wild-type-treated wild-type microglia stained for caspase-1. LPS/ATP-treated wild-type microglia served as positive control. h, Quantification of data from g. n = 7 for primed, n = 8 for tau monomers and fibrils, n = 4 for tau oligomers. *P = 0.0458, **P = 0.0091. i, Jess-based analysis of conditioned medium of primary wild-type, Asc–/– and Nlrp3–/– microglia primed with LPS and treated with the indicated forms of tau P301S. LPS/ATP-treated wild-type microglia served as positive control. Samples were stained for caspase-1. j, Quantification of data from i. n = 7 for primed and fibrils, n = 6 for monomers, *P = 0.0128. For gel source data, see Supplementary Fig. 1. All graphs are presented as mean ± s.e.m. and were analysed by one-way (a, b, h, j) or two-way ANOVA (c–f) followed by Tukey’s test. Source Data