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Fig. 7 | Acta Neuropathologica Communications

Fig. 7

From: Therapeutic antibody targeting microtubule-binding domain prevents neuronal internalization of extracellular tau via masking neuron surface proteoglycans

Fig. 7

DC8E8 targeting MTBD inhibits AD tau neuronal uptake via masking binding sites to heparan sulfate proteoglycans. a Co-localization of sarkosyl-insoluble AD tau PHFs and heparan sulfate in primary neurons. AD tau PHFs were fluorescently labelled with Alexa Fluor 594 (red) and added to cultured media. After 20 h neurons were fixed and immunostained with antibody against heparan sulfate (green, 10E4). Neurons were counterstained with DAPI (blue, nuclei) and confocal microscopy images were captured. Scale bar, 10 μm. b Representative distribution of mean fluorescent intensity (arbitrary units) in neurons treated with AD tau Alexa 488 (100 nM) for 24 h in the presence of control antibody DC51 (blue), DC8E8 antibody (red), heparin alone (pink) or heparin in combination with DC8E8 (beige) measured by flow cytometry. A left shift (blue – pink) indicates decrease in AD tau neuronal internalization in the presence of heparin (implies requirements of heparan sulfate proteoglycans) to similar extent as DC8E8-mediated inhibition of the internalized AD tau (red). Non-significant difference in the distributions of heparin alone (pink) and heparin with DC8E8 (beige) was detected. Non-treated Control neurons are indicated in grey. c Quantification of AD tau Alexa 488 internalization (100 nM, 24 h) in the presence of Control or DC8E8 antibody (1 μM), heparin (5 μM) or heparin with DC8E8 determined by flow cytometry. Experiments were performed in duplicates with a minimum of 3 independent measurements and expressed as mean ± SEM. Statistically significant change between groups stated as *p < 0.001. Flow cytometry experiments include a minimum of 10.000 events per each sample showed

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