Fig. 8: Tau oligomerization in a tauopathy mouse model is normalized upon the loss of Tuba4a C-terminal polyglutamylation.

A Immunohistochemical analysis of subcellular Tau oligomerization in layer V of cortical brain sections derived from 12-month-old Tuba4a (+/+) and (p/p) mice crossed with hTau (+/p) mice. Wild-type sections not expressing hTau, served as antibody control. TOMA-1 (red): specifically detects oligomerized human Tau. DAPI (blue): nuclei. Scale bar, 10 µm. B, C Quantification of oligomerized hTau-positive accumulations (B) and signal intensities (C) normalized to the total area/cell analyzed, shown in (A). WT set to 1; n = 3(WT), 4(+/+ and p/p) mice per genotype. D Western blot analysis depicting hTau, separated using a semi-denaturating-PAGE to preserve protein oligomerization derived from cortical lysates from 12-month-old mice, genotypes are indicated. E Quantification of the ration of low and high molecular weight (MW) hTau signal intensities, as shown in (D). Note, the abundance of high MW hTau is normalized in the genetic background of Tuba4aΔpolyGlu. hTau mice (dark gray condition) set to 1; n = 6 mice per genotype. F Dot blot analysis using cortical lysates from 12-month-old mice probed with TOMA-1 (oligomerized Tau), hTau (total human Tau) and GAPDH (loading control), genotypes are indicated. G Quantification of hTau signal intensities normalized to GAPDH. hTau mice (dark gray condition) set to 1; n = 6(+/+), 5(p/p) mice per genotype. H Quantification of TOMA-1 (oligomerized human Tau) signal intensities normalized to hTau (total human Tau). hTau mice (dark gray condition) set to 1; n = 6(+/+), 5(p/p) mice per genotype. Two-sided Kruskal Wallis test (B, C), Mann Whitney test (E, G) and unpaired Student’s t-test (H) were used to assess statistical significance. *p < 0.05, **p < 0.01. Data represent mean ± SEM. Source data, including exact p-values, are provided as a Source Data file.