Fig. 6.

Human slice cultures are responsive to WZ4003 treatment. a Cartoon illustrating the work flow for generating human brain slice cultures (HBSCs) from surplus access tissue from neurosurgical procedures. b MAP2 (green) and DAPI (blue) staining shows intact neuronal cell bodies and neurite processes in 14 div HBSC (scale bar = 50 μm). c Representative Western blot from 14 div HBSC showing total tau (tau5), p-tau Ser356, PSD95, Tuj1 and housekeeping protein cyclophilin-B. d WZ4003 does not significantly alter levels of tau (normalised to cyclophilin) (t₍₄₎ = 0.43, p = 0.688). e There is a trend for WZ4003 treatment to reduce p-tau Ser356 (normalised to cyclophilin) (t₍₄₎ = 2.43, p = 0.072). f There is a trend for WZ4003 to reduce the ratio of p-tau Ser356/total tau (t₍₄₎ = 2.17, p = 0.096). g WZ4003 treatment significantly increased Tuj1 levels (*t₍₄₎ = 3.39, p = 0.028). h WZ4003 does not significantly alter tau levels as a proportion of neuronal protein (t₍₄₎ = 2.04, p = 0.11). i WZ4003 significantly lowers p-tau Ser356 as a proportion of neuronal protein (**t₍₄₎ = 4.81, p = 0.0086). j There is a trend for WZ4003 to increase PSD95 protein (normalised to cyclophilin) (t₍₄₎ = 2.37, p = 0.077). k There is no effect of WZ4003 on PSD95 protein (normalised to Tuj1) (t₍₄₎ = 0.74, p = 0.501). N = 5 cases per condition. Each point represents an individual human case, triangles = males, circles = females. Cartoons generated using BioRender