Fig. 4

Aβ oligomers potentiate intracellular tau aggregation by promoting tau seed uptake. a, b Fluorescence-microscopy images (a) and flow cytometry-based quantification (b) of internalized fluorescein-labeled tau seed (500 nM, green) in SH-SY5Y cells with or without pretreatment with 200 nM freshly prepared, oligomeric, or fibrillar Aβ. Untreated SH-SY5Y cells were used as a negative control. After extensive PBS washing, cells were fluorescently imaged and subsequently harvested with trypsin treatment for flow cytometry. The data are presented as mean ± SD (n = 8, ****p < 0.0001, one-way ANOVA). The scale bar denotes 20 μm. c Various concentrations of heparin, from 10 nM to 50 μM, were applied to HEK293T tau biosensor cells 1 h before Aβ pretreatment, and tau seeding was quantified as integrated FRET density using flow cytometry. d The same trend of Aβ-oligomer mediated enhancement of labeled tau seed internalization in HEK293T cells. Heparin was added 1 h before Aβ pretreatment. The data are presented as mean ± SD (n = 6). e A diagram of Aβ-promoted tau seeding