Fig. 7

GVBs independently induced by tau and α-synuclein pathology are p-tau217-positive. a–c Immunofluorescence co-staining for CK1δ (magenta) and p-tau217 (green) in our experimental GVB models. Separate channels are shown in greyscale and nuclei are visualised with DAPI (blue) in the merged images. a Representative confocal images of GVB+ neurons in the FTDtau¹⁺² model show a strong overlap between CK1δ puncta and p-tau217 in addition to the cytosolic tau pathology also marked by the phospho-tau epitope. Several examples with varying levels of somatic pathology are shown for better visualisation b Representative confocal images of a GVB+ neuron in a staining control condition for which p-tau217 primary antibody was omitted. c Representative confocal images of a GVB+ neuron in the seeded α-syn pathology model show a similar overlap between GVB markers as observed for the tau/GVB model in the absence of signal for somatic tau pathology. d Schematic summary: GVBs are inseparably associated with pathological protein accumulations and can be independently induced by cytosolic tau and α-syn pathological protein assemblies. Neurons with advanced tau pathology in the human brain are devoid of GVBs. In contrast, GVBs are observed in neurons with advanced α-syn pathology. Our data indicate that GVBs are a generalised lysosomal response to disturbed proteostasis