Fig. 5

Tau pathology and clearance deficits in two primary neuron models of tauopathy. a Immunofluorescence images of MC1 (pathological tau—red) and α-tubulin (microtubules—white) in DIV 15 (days of culture) cortical neurons from PS19 mice (overexpressing human tau P301S) exposed to DS1 seeds (upper panel) or to DS9 seeds (lower panel). Scale bar represents 30 μm. b Co-localization between MC1 (red) and p62 (green) in DIV 15 neuronal dendrites (labelled with Map2, white) from PS19 cortical neurons exposed to DS9 seeds. Scale bar represents 10 μm. c Rat neurons treated with a lentivirus overexpressing the tau repeat domain tagged with yellow fluorescent protein (TauRD-YFP) showing immunofluorescence images of tau tagged with YFP (red), p62 (green) and Map2 (white) in DIV 18 cortical neurons exposed to WT mouse brain lysate (upper panel) or rTg4510 (overexpressing human tau P301L) brain lysate (lower panel). Notice the aggregation of TauRD-YFP in the presence of pathological brain lysate. Scale bar represents 30 μm. d–f Images showing that increasing doses of pharmacological inhibitors of the proteasome—epoxomicin (1 to 20 nM) or MG132 (10 nM to 1 µM)—triggered an increase of the percentage of neurons with TauRD-YFP inclusions. Images are shown for epoxomicin. Scale bar represents 30 μm  (e); quantification is shown for both (e–f)