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. Author manuscript; available in PMC: 2021 Oct 5.
Published in final edited form as: Cell Rep. 2021 Sep 21;36(12):109720. doi: 10.1016/j.celrep.2021.109720

Figure 4. Reduction of P301L tau and ASC reduces inflammasome markers and tau pathology in rTg4510 and hTau/ASC−/− mice, respectively.

Figure 4.

(A–D) qRT-PCR analysis show DOX treatment from 3–6 months in rTg4510 mice significantly reduced the mRNA expression of ASC, NLRP3, and IL-1β; protein levels of ASC, NLRP3, and modest reduction in IL-1β.

(E–H) DOX treatment from 5–9 months in rTg4510 mice showed modest reduction in mRNA for only ASC and significant reduction in protein levels of ASC, NLRP3, and IL-1β in the hippocampi.

(I) Western blot analysis and quantification for 6-month-old hTau/ASC−/− mice show significantly reduced PHF1+ (phosphorylated at ser396/ser404) in the hippocampi compared to age-matched hTau mice. ELISA analysis shows 10-fold reduction in the IL-1β levels in the hippocampi of 6-month-old hTau/ASC−/− mice.

(J) Significant reduction in the percentage of AT8+ area in the CA3/dentate gyrus of 6-month-old hTau/ASC−/− mice compared to age-matched hTau mice. Scale, 50 μm.

(K and L) Novel object recognition test shows hyperactivity and equal object preference for 6-month-old hTau mice (see representative heatmap of exploration in K) and significant impairment in distinguishing novel object from familiar object (ratio of encounters with novel object within 5 min) on the test day. This is rescued in 6-month-old hTau/ASC−/− mice.

Data displayed as mean ± SEM, unpaired Student’s t test, *p < 0.05, **p < 0.01, ***p < 0.005, n = 4–6 (B and D); n = 5–9 (F and H); n = 3–5 (I), or one-way ANOVA followed by Tukey multiple comparison test, *p < 0.05, n = 4 (J); two-way ANOVA followed by Sidak’s multiple comparison test, *p < 0.05, ***p < 0.005, n = 21 for non-Tg; n = 16 for hTau; n = 7 for hTau/ASC−/− (K and L).

See also Figures S4, S5, S6, and S7 and Data S1.