Fig. 2.

Neuronal tau pathology in R962-hTau rats.

Tau pathology between 10 and 20-months of age (n = 8–9/group). (A) Early tau pathology may be seen at 10-months with phosphorylation-dependent antibody CP13 (top left) and conformational-dependent antibody MC1 (top centre). At the 18–20-month time point, there is extensive recruitment of endogenous tau, observed with T49-immunoreactivity, to tau inclusions throughout the cortex (top right). Later time points revealed ballooning neurons in the pyramidal cells of the cortex, immunoreactive for CP13, MC1, T49 and PHF1 (middle panels; bottom left panel). Some animals also develop AT180-immunoreactivity globose NFT that occur in the upper horn of the dentate gyrus granular cell layer (bottom centre). Immunofluorescence with HT7 (green) demonstrate the presence of tau burdened neurons (small arrowheads), dystrophic neurites (arrows) and an extraneuronal tangle, where no nuclear signal is observed with DAPI (bottom right). (B) Silver impregnation using modified Bielschowsky method reveals numerous silver positive inclusions at 15-months old in the R962-hTau cortex and CA1 region of the hippocampus, whilst the control cortex and CA1 are devoid of silver aggregates. Right hand panels demonstrate axons, plaque neurites and tangles in tissue from the inferior temporal lobe (IT) of a subject with AD (n = 2/group). Scale bars 25 μm.