Fig. 1

Pathological tau accumulation is a prerequisite for GVB formation in the FTDtau¹⁺² model. a Schematic representation of the protocol to induce seed-independent intraneuronal tau pathology in primary mouse neurons. WT neurons were plated at DIV 0. At DIV 3, neurons were transduced with FTDtau¹⁺². Cells were fixed and analysed by immunofluorescent staining for pathological tau and GVBs at DIV 18. b Representative confocal images of FTDtau¹⁺²-transduced tau+/GVB+ neuron (left) and a tau−/GVB− untransduced neuron (right) shown as control. Immunofluorescence staining was performed for the neuron-specific dendritic marker MAP2 (grey), MC1 (green) and pPERK (magenta). Separate channels are shown in greyscale. c, d Representative confocal images of GVB+ neurons in the FTDtau¹⁺² model. Co-immunofluorescence staining was performed for the canonical GVB marker CK1δ (magenta) and the additional GVB core marker pPERK (c) or the GVB membrane marker LIMP2 (d) (green). Nuclei are visualised by DAPI (blue). Separate channels are shown in greyscale and in colour in the merge. A line intensity profile along the white bar indicated in the merge shows CK1δ co-localisation with pPERK and that is surrounded by LIMP2 as additional GVB markers. e Density plot of single-cell somatic Log2-transformed corrected mean MC1 immunofluorescence intensity of tau−/GVB− (grey) and tau?/GVB+ (pink) neurons in the FTDtau¹⁺² model. N=3 independent experiments, n=55 and 60 for tau−/GVB− and tau?/GVB+ populations, respectively. ****p < 0.0001, Kolmogorov-Smirnov test for not normally distributed data