Fig. 6: Oligomeric tau is close enough to clusterin to be a binding partner within postsynapses in PSP brain.

a, A single 70 nm segmented array tomography section of PSP frontal cortex immunostained for oligomeric tau (T22, magenta), clusterin (CLU, yellow) and postsynapses (PSD95, cyan). Scale bar = 10 μm. Insets show colocalization and positive FRET signal between clusterin and oligomeric tau and oligomeric tau and PSD95 within a postsynapse. Scale bar for FRET images indicates intensity (0–255 a.u.). b, As predicted from the proteomics results, colocalization of clusterin and PSD95 was higher in PSP than in control (PSP, n = 7 control and n = 10 cases, two to four image stacks per case as technical replicates, LMEM on Tukey transformed data ~ diagnosis + (1 | case), Tukey-corrected post hoc pairwise comparison estimate = 0.646, 95% CI (0.323, 0.956), t(12.2) = 4.743, P = 0.0005). c, In PSP frontal cortex, PSD95 and T22 generate a FRET signal significantly different from 0 (one-sample t-test on means per case with μ = 0, t = 10.12, df = 4, Bonferroni-corrected P = 0.0010). Similarly, within postsynapses positive for both T22 and clusterin, these proteins generate a FRET signal (t(5) = 14.644, Bonferroni-corrected P = 0.00005), indicating these proteins are likely interacting within synapses. Boxes show the first quartile, median and third quartile of the stack data. Whiskers show minima and maxima without outliers. Data points show case means (females, circles; males, triangles).