Fig. 3.

Tau from AD brains induces inhibitor-insensitive tau pathology in wildtype and LRRK2^G2019S neurons. A) Schematic diagram of AD PHF tau extraction from human brain tissue and subsequent treatment of primary neurons. B) Primary hippocampal neurons from NTG or LRRK2^G2019S mice were treated with vehicle or LRRK2 inhibitors at 300 nM at 5 DIV. They were further treated with AD PHF tau at 1μg/mL at 7 DIV, and both fixed and stained for insoluble mouse tau (T49, magenta) and DAPI (gray) at 21 DIV. Scale bar = 15μm. C) Quantification of the insoluble mouse tau area/nuclei number in each condition. No insoluble tau was present in the absence of PHF treatment and there was no overall effect of genotype (Two-way ANOVA; genotype effect p = 0.837, Dunnett’s multiple comparison test within genotype: NTG: DMSO-PHF vs. DMSO ^****p < 0.0001; DMSO-PHF vs. MLi-2 ^****p < 0.0001; G2019S:: DMSO-PHF vs. DMSO ^****p < 0.0001; DMSO-PHF vs. MLi-2 ^****p < 0.0001; all other values were not statistically significant, n (separate cultures) = 15 independent samples/group). Data are represented as mean±SEM with individual data points plotted.